[CANCER RESEARCH 47, 2092-2097, April 15, 1987]
Secretory Epithelial Cell Marker on Gastrointestinal Tumors and in Human
Secretions Defined by a Monoclonal Antibody1
Wolfgang G. Dippold,2 Reinhard Klingel, Helga Bernhard, Hans-Peter Dienes, Alexander Knuth,
and Karl-Hermann Meyer zum Büschenfelde
¡.Medizinische Klinik [W. G. D., R. K., H. B., A. K„K-H. M. z. B.], and Pathologisches Institut [H-P. D.}, Johannes Gutenberg Universität,Langenbeckstrasse l,
D-6500 Mainz, W. Germany
ABSTRACT
A new marker for human secretory epithelial cell types (Exo-1) has
been defined by a mouse monoclonal antibody (Pa-G14). The antibody
was raised against a human exocrine pancreatic tumor cell line (Capan1) and tested against 46 cultured human cell types and 228 freshly frozen
human tissue sections. It reacted specifically with 28 normal and 55
secretory neoplastic epithelial tissues tested. Eleven different secretory
epithelial cell types expressed this antigen, as well as human fetal tissues
of the gut and bronchi. One hundred and twenty samples of normal
tissues, cells, and tumors of nonexocrine origin were Exo-1 negative. In
normal secretory tissues staining was most pronounced at the apical poles
and as shown by immunoelectron microscopy in the case of the duodenum,
at the microvilli. In cultured Exo-1 positive tumor cells the antigen was
not demonstrable on the cell surface but in the cytoplasm after acetone/
methanol fixation only. The antigen was identified biochemically as a
polar neutral glycolipid and detected in human salivary, bronchial, pan
creatic, and intestinal secretions by an enzyme-linked immunosorbent
assay, but was not found in sera of healthy controls or patients with
gastrointestinal and other tumors.
Antigen Exo-1 represents a novel common antigen for normal and
tumorous glandular epithelial cells.
INTRODUCTION
The analysis of tumor associated antigens has advanced a
great deal by the application of monoclonal antibodies (1) in
recent years. One of these antigens, the GD3ganglioside, which
has proved to be restricted to tumors and cells of neuroectodermal origin (2-4), may even gain therapeutic importance (5, 6)
besides being useful for immunohistochemical diagnosis (3, 4).
More recently, studies were undertaken in our laboratory to
define new antigens for gastrointestinal cancers. Because early
detection of pancreatic cancer is still an unsolved problem, our
current efforts are concentrated on this tumor. There are nu
merous reports on the definition of pancreas tumor associated
antigens. Most of these antigens had been defined by polyclonal
heteroimmune sera (7-14), and therefore the analysis of such
an abundance of epitopes as on pancreatic cancer cells remained
incomplete. After the introduction of hybridoma technology
(1), a number of novel antigens on gastrointestinal tumor cells
defined by monoclonal antibodies have been described. One of
them, Ca 19-9, was originally isolated for its reactivity with
human colon cancer cells (15), but it has since been shown to
also react with gastric and pancreatic cancer tissues, with spec
imens of normal pancreas (16, 17), and with sera from patients
with gastric and pancreatic cancer (18). The DU-PAN series of
monoclonal antibodies (19) was elicited against the human
pancreatic cell line HPAF. The tissue specificity of DU-PAN2 antigen (20) and its presence in serum and ascites of patients
with adenocarcinoma (21 ) has just been reported. Several more
pancreatic cancer reactive monoclonal antibodies have been
raised (22-27). Two of them seem to differentiate between
acinar and ductal cell characteristics in benign and malignant
pancreatic tissue (22, 23). All other monoclonal antibodies
differ from each other and show a rather close or more distant
association with pancreatic cancer, but final evaluation is not
yet possible (24-27).
In this study we report on a novel antigen on pancreatic
tumor cells, which is common to most neoplastic and normal
secretory epithelial cell types and is characterized biochemically
as a polar neutral glycolipid and found in human secretions.
MATERIALS AND METHODS
Development of Monoclonal Antibody Pa-G14. BALB/c mice were
immunized biweekly with 1.5-3 x 10' mechanically scraped tumor cells
of the cultured human exocrine pancreatic tumor cell line Capan-1 (4).
Freund's adjuvant (0.5 ml) was added to the tumor cells for the first
immunization only. The mice were immunized 4 times i.p. and in
addition i.v. the last time. Monoclonal antibodies were generated as
described (2). Culture supernatants of hybridomas were screened ini
tially on a panel of 14 live and acetone:methanol (by volume, 2:1) fixed
cultured human cell lines (2, 28) consisting of 2 pancreas, 2 colon, 2
kidney, and 2 lung cancers, 2 melanomas, 2 astrocytomas, and on
normal fibroblasts and kidney epithelium cultures. Hybridoma culture
Pa-G14 produced antibody which reacted with the 2 pancreatic tumors
(Capan-1, ASPC) only. This culture was selected and cloned 3 times.
A single large batch of Pa ( ì
14 monoclonal antibody (IgM) was col
lected, concentrated 5:1, and used at an Ig concentration of 250 Mg/ml
for final analysis on a panel of 46 cultured tumor and normal cell types
by indirect immunofluorescence, using I (ah)., rabbit anti-mouse Ig,
diluted 1/20 (Dakopatts, Copenhagen, Denmark) as second antibody
and on 228 freshly frozen tissue sections by indirect immunoperoxidase.
Cultured human tumor cells were also tested with sera of nude mice
growing Pa-G14 hybridoma cells. The cultured cell lines were obtained
partly from Drs. L. Old and J. Fogh of the Memorial Sloan-Kettering
Cancer Center in New York, NY and the biliary carcinomas Mz-ChA1,2 (29) and the liver cell carcinoma Mz-Hep-1 (30) that have been
established recently in our laboratory. Absorption tests were performed
as described (2). Neuraminidase was derived from Vibrio cholerae and
used at 1 unit/ml (Behring Werke, Marburg, West Germany).
Immunocytochemical Analysis. Frozen tissue sections (5 /un) were
prepared, tested by an indirect immunoperoxidase method, and counterstained with Mayer's hemalum solution (3). Immunoelectron micro
graphs of tissue were performed as described (31). No background
staining was observed with monoclonal antibodies to the mouse lym
phocyte antigen Lyt-1.1 (IgM) and the monoclonal antibody R-24 (Igy,)
to ganglioside <.,,< on melanoma cells (32), which served as negative
controls.
Glycolipid Extraction. Glycolipids were isolated from l g of tissue or
cell pellet and from 2 ml of bronchial and pancreatic fluid by a
modification of the method of Saito and Hakomori (33) and separated
by DEAE-Sephadex in neutral and acidic forms (34) as described (32).
Received 8/4/86; revised 12/19/86; accepted 1/14/87.
The costs of publication of this article were defrayed in part by the payment
The neutral glycolipid fraction of cells and tissues was dissolved in 1
of page charges. This article must therefore be hereby marked advertisement in
ml and of bronchial and pancreatic fluid in 100 //I chloroaccordance with 18 U.S.C. Section 1734 solely to indicate this fact.
form:methanol:H2O (10:10:1). Aliquots (6 ¿il)were applied to high' Supported by grant Di 24S/3-3 from the Deutsche Forschungsgemeinschaft
performance thin-layer chromatogram-silica gel plates; Merck, Darm
and the Bundesministerium für
Forschung und Technologie.
2To whom requests for reprints should be addressed.
stadt, West Germany). Solvents used for developing chromatograms
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EPITHELIAL
CELL MARKER DEFINED
were chloroform:methanol:H2O (65:25:4). Once the solvent had mi
grated 7 cm from the origin, the plate was air dried for 10 min, placed
in n-hexane 2% Plexigum for 2 min, and dried again. Then the plates
were immunostained with mAb3 Pa-G14 (250 jig/ml) according to a
modification of the method of Magnani et al. (35) using peroxidase
labeled rabbit anti-mouse antibody, 1/20 diluted (Dakopatts, Copen
hagen, Denmark) as second antibody and 4-chIoro-l-naphthol (Sigma,
St. Louis, MO) as substrate. Forty mg chloronaphthol were dissolved
in 0.5 ml ethanol and 100 ml 0.05 M Tris-buffer, pH 7.6, the mixture
filtered, and 100 >i\H2O2 (30%) added just before incubating the plates
for 10-20 min. The immunostaining was developed and thereafter the
neutral glycolipid standard, kindly provided by Drs. Felding and Wiegandt, Marburg, West Germany, was stained by orcin.
Pa-G14 Antigen ELISA. For the detection of antigen in body fluids
an ELISA was developed. Equal volumes of centrifuged (10,000 x g/
30 min) serially diluted secretions and chlorofornrmethanol (2:1) were
mixed. This solution was centrifuged (1,000 x g/\Q min) whereby it
separated into 2 phases. The upper phase was coated to microfluor "w"
plates (Dynatech, Alexandria, VA) and exsiccated. In order to reduce
nonspecific binding, plates were rehydrated with 200 /jl phosphate
buffered saline plus 5% fetal bovine albumin overnight; then 50 ¡i\mAb
(250 Mg/ml) were incubated for l h at 4°C.Following 2 washes of 0.5
h each with phosphate-buffered saline plus 0.1 % bovine serum albumin,
100 ¿ilof /3-galactosidase-labeled F(ab)2 rabbit anti-mouse antibody
(Zymed, Burlingame, CA), appropriately diluted (1:500) in RPMI plus
5% human serum albumin were incubated for 45 min. Two hundred 4methylumbelliferyl-/3-D-galactoside (1 mg dissolved in 59 ml phosphatebuffered saline, pH 6.9; Sigma) were added to the washed plates and
incubated for another 30 min at 37°C.Afterwards the samples were
evaluated in a Dynatec microfluor reader.
BY MONOCLONAL
ANTIBODY
Table 1 Reactivity of mAb Pa-G14 with in vitro cultured human cells by indirect
immunofluorescence
Antibody l'a d 14 supernatants (Ig concentration, 250 ¿tg/ml)yielded the same
results as nude mouse sera (data not shown, titers 1/50 up to 1/800).
Reactivity titer
typePancreas Cell
Capan- 1, ASPC-1
Capan-2
Colo-357Fixed
Biliary
Mz-ChA-1
Mz-ChA-2
SK-BL-1
Liver
Mz-Hep-1
SK-Hep-l,PLC/PRF/5
Colon
SK-CO-12
SK-CO-10, 11, 13
SW-1083, HT-29
Live
by
acetone:methanol
(2:1) for
min1/8
15
1/4
1/4
1/4
I/I
1/8
1/4
Breast
SK-BR-3, AlAb
BT-20, MCF-7
Lung
Mz-Lu-1
SK-Lu-3, 12, 14
Renal
SK-RC-6, 7, 9, 11
Cervix
ME-180
RESULTS
Pa-G14, a Secretory Epithelial Tissue Antigen. At first the
specificity of monoclonal antibody Pa-G14 was determined on
a panel of 46 different human cultured cell lines (Table 1). Both
live and acetonermethanol fixed cells were tested. Reactivity
was found with acetone:methanol fixed secretory epithelial
neoplastic cell types only (Fig. 1). The antigen was localized in
the cytoplasm of in vitro cultivated human tumor cell lines of
the exocrine pancreas (Capan-1, Capan-2, Colo-357, ASPC-1),
the liver (Mz-Hep-1), the biliary tract, (Mz-ChA-2, SK-BL-1),
and the colon (SK-CO-12).
Finally the tissue specificity of mAb Pa-G14 for secretory
epithelial cell types was established on 228 human fresh frozen
tissue samples of normal (n = 121), fetal (n = 8), and neoplastic
origin (n = 99). Twenty-eight normal exocrine tissue samples
(Table 2) and 55 adenocarcinomas of the 70 epithelial tumors
tested reacted with Pa-G14 (Table 3). Most of the adenocarci
nomas were derived from the gastrointestinal tract. In particular
the apical poles of the acinar cells in the normal exocrine
pancreas, the stomach, gallbladder, uterus, prostate, urinary
bladder, bronchi, and the duodenum (see Fig. 2), including
Brunner's glands, showed the strongest immunohistochemical
staining. The distinct apical staining of the duodenal microvilli
was best documented by immunoelectron microscopy (Fig. 2c).
Epithelial of the salivary glands, breast, colon, and prostata
also reacted with mAb Pa-G14, while hepatocytes of 6 different
liver specimens did not. A clear difference was noted between
the goblet cells of the duodenum and those of the colon. While
those in the duodenum reacted with mAb Pa-G14, the goblet
cells in the colon did not. The Pa-G14 positive cells in the
colon were the absorptive cells. All epithelial cells lining ducts
or ductules examined in the parotis, pancreas, and breast did
3 The abbreviations used are: mAb, monoclonal antibody; ELISA; enzymelinked immunosorbent assay.
Bladder
T-24
Testis
SK-GR-1
Melanomas
SK-MEL-19, 28, 29, 37,61,
64
Astrocytomas
SK-AJ, AS, AN
Neuroblastoma
SK-NHC
Lymphoblastoid cells
T-cell, T-45
B-cell, Daudi
Epstein-Barr virus B-cells 1, 2
Normal cells
Kidney epithelium I, 2
Fibroblasts 1, 2
not stain with mAb Pa-G14. In some small ductules, however,
Pa-G14 reactivity was observed in the lumina. This was most
likely due to positive secretions and not due to a positive
staining of the epithelial cells lining the ductules. Tumor sam
ples that revealed positive immunoreactivity included 8 of 8
exocrine carcinomas of the pancreas, 12 of 12 adenocarcinomas
of the stomach, 6 of 6 of the bile tract, 18 of 18 of the colon,
and 8 of 8 of the breast. As an example, the immunohistochem
ical staining of an exocrine carcinoma of the pancreas is shown
in Fig. 3 and the immunocytochemical staining of tumor cells
in the malignant ascites of a patient with ovarian carcinoma in
Fig. 4. In contrast to normal tissues, where all secretory cells
in a given tissue sample reacted with antibody Pa-G14, in tumor
samples only a percentage of tumor cells reacted. The percent-
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EPITHELIAL CELL MARKER DEFINED BY MONOCLONAL
ANTIBODY
Table 3 Immunohistochemical reactivity ofmAb Pa-Cl4 with frozen sections of
human tumor tissues
Epithelial tumors,
type8/8 tissue
staining
(%)"10-100%10-100%80%10-80%30-10
pancreas6/6
duct1/2
bile
liver2/2
esophagus12/1
stomach18/1
2
colon8/8
8
breast1/1
bronchus1/3
kidney1/1
urothel2/2
ovary4/4
thyroid3/3
basal cell epitheliomamAbPa-G14
°The percentage of Pa-G14 positive tumor cells in a given tissue section. The
Pa-G14 reactivity also varied from reactive to strongly reactive. Nonepithelial
negative tumors included 19 melanomas, 2 neurinomas, 1 chondroma, 2 liposarcomas, I osteosarcoma, 1 seminoma, 1 insulinoma, 1 carcinoid tumor, and 1
mesothelioma.
Fig. 1. l'a (i 14 reactivity of cultured, human, methanolracetone (2:1) fÃ-xed
exocrine pancreatic tumor cells (Capan-1) by indirect immunoperoxidase. Only a
percentage of cells stained positive, x 270.
Table 2 Immunohistochemical reactivity ofmAb Pa-Gl4 with frozen sections of
normal human tissues
Tissue
Reactivity
Exocrine
Exocrine pancreas (4);°
salivary glands (2); breast (3);
prostate (1)
++*
+
++
Glandular epithelia of
Esophagus (1);
stomach (7); duodenum (2);
colon (3);
gallbladder (1);
bronchi (2);
uterus (1);
bladder epithelium ( 1);
liver (6)
+
++
+
++
++
++
++
—
Endocrine
Pancreas (4); adrenals (2); thyroid (1); parathyroid (1)
Neural
Cerebrum (2; gyrus postcentral); cerebellum (I); peripheral nerve (2)
Hematological tissues and cells
Thymus ( 1); lymph nodes ( 10); tonsills ( 1); spleen (2);
bone marrow (2); leukocytes (2); RBC (A, B, O); T- (2),
B-(2)
—
-
Other
Muscle: smooth (6); skeletal (4);
connective (10); fat tissues (5);
skin (10); nevi (7); kidney (2);
ureter (I); urethra (1);
testis (1); epididymis(l); ovary (1)
—
—
•
Numbers in parentheses, number of specimens tested.
* Degree of staining: +-t-, strong; +, positive; —,no staining. Secretory cells in
a given normal tissue sample were always all m Mi Pa-G14 positive.
age of Pa-G14 positive tumor cells ranged from 10-100% of
all exocrine tumor samples tested. Histológica! grading did not
correlate with the percentage of Pa-G14 positive tumor cells in
the tissue specimen examined.
Pa-G14 immunoreactivity could also be demonstrated in the
gut and lung of human fetal tissues (12 weeks after gestation).
Human fetal brain, cerebellum, thymus, kidney, spleen, and
liver lacked Pa-G14 reactivity.
One hundred and twenty normal tissue and tumor specimens
of endocrine, neural, and hematopoetic origin as well as normal
connective, muscle, and adipose tissues and blood vessels were
Pa-G14 negative (Table 2). In addition a group of normal
epithelia (liver, kidney, ureter, urethra, skin, testis, ovary, and
thyroid) did not react.
Pa-G14 positive tissues retained their reactivity after fixation
with acetone:methanol but lost most of it after fixation with
3.3% formalin. The staining pattern and intensity of the acetone:methanol fixed sections were comparable to the corre
sponding freshly frozen samples.
To exclude blood group specificities, not only were RBC of
A, B, and O type tested in absorption tests (2) but also purified
preparations of human blood groups A, B, and O, Le" glycoproteins, and pneumococcal XIV polysaccharide (obtained from
Dr. Kabat through Dr. K. Lloyd). All samples were negative as
were carbohydrate extracts isolated from human milk (36)
supplied by Dr. Egge and examined by absorption tests.
Pa-G14, a Polar Glycolipid. To assess the nature of the target
molecule detected by mAb Pa-G14, heat stability and neuraminidase sensitivity of the antigen were tested on the pancreatic
carcinoma cell line Capan-1 by absorption tests. The antigen
proved to be heat stable, insensitive to neuraminidase, and not
demonstrable by sodium dodecyl sulfate-gel electrophoresis and
immunoblotting. Therefore preparations of normal human pan
creas and the human pancreatic tumor cell line Capan-1 were
extracted with chloroform:methanol:H2O
to obtain the glycolipid fraction. Glycolipids were separated into neutral and acidic
fractions by DEAE-Sephadex chromatography and then iden
tified by thin-layer chromatography. A distinct band was de
tected by mAb Pa-G14 in the neutral glycolipid fraction of
normal pancreatic tissue and the pancreas cancer cell line
Capan-1 in bronchial lavage and pancreatic fluid but not in the
glycolipid fractions of human brain, spleen, and liver (Fig. 5).
The newly defined neutral glycolipid molecule, characteristic of
secretory epithelial cells, appears to be a polar molecule accord
ing to its mobility in thin-layer chromatography.
Pa-G14 Antigen in Secretions. Because antigen l'a ( i 14 was
localized to the apical surface of the intestinal microvilli by
immunoelectron microscopy and extracted from pancreatic and
bronchial fluids, an ELISA was developed. Specific reactivity
ofmAb Pa-G14 was demonstrable in this ELISA with 12 of 12
samples of human saliva, bronchial, intestinal, and pancreatic
fluid, but not with 6 of 6 normal human serum samples (Table
4). In addition 20 sera of patients with gastrointestinal tumors,
12 of them carcinoembryonic antigen positive, and 8 patients
with advanced pancreatic carcinoma were Pa-G14 negative.
Sera of 12 patients with nonepithelial tumors also did not react.
These included 8 patients with malignant melanoma and 4 with
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EPITHELIAL
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ANTIBODY
Fig. 3. Immunohistochemical
Pa-G14 (arrows), x 120.
staining of a pancreatic carcinoma with mAb
•'*
«fc
%
Fig. 4. Immunocytochemical staining of the tumorous ascites cells (arrows) of
a patient with ovarian carcinoma. Magn. There is a different staining effect for
fixed in vitro cultured exocrine pancreas cells (Fig. 1, peripheral staining) and the
tumorous ascites cells shown here (central staining), x 200.
DISCUSSION
Mouse monoclonal antibody Pa-G 14 defines a novel common
antigen for human secretory epithelial cells (Exo-1), which was
identified biochemically as a neutral, polar glycolipid molecule.
Exo-1 therefore represents another example for a glycolipid
molecule which characterizes certain human tissue types. Re
cently the authors had defined the ganglioside GD.Ias a marker
for neuroectodermal tumors, particularly human malignant
melanomas (2-4). The tissue distribution of this new glycolipid
antigen Exo-1 is different from known markers of glandular
epithelia, such as "secretory component" (37, 38), epithelial
Fig. 2. Immunohistochemical staining with mAb Pa-G 14. a. exocrine pancreas
tissue Pa-G 14 positive, islet cells negative, x 120. h. Pa-G 14 positive (j ).duodenal
epithelium, by light microscopy, x 120. c, Pa-G 14 positive apical surface staining
of the duodenal microvilli (J ) by immunoelectron microscopy, x 19,000.
acute myeloid leukemia. Other mAbs defining mouse lympho
cyte antigens and human melanoma antigens used as negative
controls proved to be unreactive.
membrane antigen EM A (39), and keratins (40, 41). The rela
tionship to a recently described marker on human ovarian
carcinoma cells remains to be determined (42). The antigen is
primarily localized in the apical region of normal Pa-G 14
positive epithelia as shown by indirect immunoperoxidase stain
ing in light and immunoelectron microscopy and can be secreted
because it is detectable in samples of bronchial lavage, saliva,
and intestinal and pancreatic fluid by ELISA. The availability
of this specific mAb will allow further studies which will deter
mine the level of secretion of this glycolipid antigen in ascites
and secretions of patients with gastrointestinal tumors in com
parison with normal individuals. In preliminary results shown
here the antigen was not found in the sera of 20 patients with
gastrointestinal tumors, in sera of 12 patients with nonepithelial
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EPITHELIAL
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ANTIBODY
genie expression observed in cultured tumor cells and normal
tissues may also be explained by the possibility that the antigen
is localized at the cell surface of neoplastic secretory epithelial
cells but not available for reaction with antibody. This phenom
enon has been found with other cell membrane glycolipids; e.g.,
globoside is a major glycolipid of the RBC membrane, but RBC
react only weakly with anti-globoside antibody (44).
Glycolipid molecules with similar biochemical properties, socalled "glucolipids," have been described by Slomiany et al. (45)
and Slomiany and Slomiany (46) in hog mucosa and in human
secretory epithelial cells (47). The antigenic epitopes, however,
between the hog glycolipids and the glycolipid, defined by mAb
Pa-G14 must be different, because mAb Pa-G14 did not react
5
with hog pancreas (data not shown). The relationship of Pa6
7 *
G14 to biochemically defined human secretory (47) glucolipids
still remains to be elucidated. Many glycolipid antigens, most
of them associated with human carcinomas and some related
a
to blood group determinants have been defined recently by a
number of investigators (for reviews, see Refs. 48 and 49). We
are now in the process of determining the biochemical structure
Fig. 5. Thin-layer chromatograms of neutral glycolipid extracts from human
of this novel glycolipid antigen. The structural relationship of
tissues: *, pancreas; d, liver; e, spleen;/ brain. Capan-1 pancreatic tumor cells (c)
this antigen to known adenocarcinoma related glycolipid anti
and bronchial fluid (g), immunostained by mAb Pa-G14 and peroxidase labeled
gens (50-54) will be of special interest.
rabbit antimouse as second antibody, a, neutral glycolipid standard, stained by
orcin: /, ceramide monohexoside; 2, ceramide dihexoside; 3 and 4, ceramide
Although Exo-l represents one of the broadest reactive imtrihexoside; 5 and 6, ceramide tetrahexoside; 7, ceramide pentahexoside.
munological markers for secretory epithelial cells to date, not
all exocrine cells are reactive with mAb Pa-G14 at the antibody
Table 4 Detection of antigen Exo-l by mAb Pa-G14 in body fluids (ELISA)
concentration used. It is not clear whether hepatocytes contain
Negative controls included in.Alii to mouse lymphocyte antigens Lyt-1.1. Lyt3.2 (IgM), and human antigens, ganglioside GDI (R-24, Igy3), HLA-Dr (Ig-yz.);
too little or whether they simply do not synthesize this glyco
lipid, which can be detected in cultured Mz-Hep-1 hepatoma
and as negative antigen controls, 6 different sera of normal individuals.
ELISA counts
cells. It also remains to be elucidated if the difference in antigen
(absorbance) dilution
expression of goblet cells in the duodenum which stain Pa-G14
of test fluid
positive and those in the colon which do not is a quantitative
HuidPancreaticBronchialIntestinalSalivaControlsSample12123456I2121/10873155013012473121531244086737993923712-501/1001755164718507925571521141414984888-48
Test
or qualitative finding. Differences in the expression of blood
group antigens A, B, and H (55) are known for the goblet cells
of the small intestine and the transverse and distal colon.
Because mAb l'a (.14 reacts with cells of fetal gut and
bronchi, this monoclonal antibody will also allow detailed stud
ies on the development and distribution of exocrine tissues in
human fetuses, especially as they relate to the development of
the apocrine secretion of these cells. The embryogenesis of the
human exocrine system and the mechanisms of exocrine secre
tion in the embryo and the adult may be explored more readily
with the aid of this marker.
3 **
4
ACKNOWLEDGMENTS
tumors, and of 6 normal individuals. These results differ from
findings obtained with Cal9-9 and DU-PAN-2 (21, 43) anti
gens, which can be significantly increased in sera of patients
with gastrointestinal tumors.
The glycolipid determinant, defined by mAb Pa-G14, is not
detectable on the cell surface of Pa-G14 positive cultured cell
lines and is accessible for antibody after fixation of the cells
only. The fixation procedure may therefore reveal cryptic anti
gens. In the case of the normal duodenal epithelium, however,
the antigen seems to be on the cell surface as shown by immunoelectron microscopy. It remains to be seen if this glycolipid
molecule is accessible for antibody in cultured normal secretory
epithelial cells. Unfortunately normal human secretory epithe
lial cell culture systems were not available to prove if this
difference in antigen localization is a feature of tumor cells
indicating a loss of the normal secretory capabilities in human
secretory epithelial tumors. The difference between the anti-
The excellent technical assistance of Birgit Schneider and Erika
Boosfeld is acknowledged.
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2097
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Secretory Epithelial Cell Marker on Gastrointestinal Tumors and
in Human Secretions Defined by a Monoclonal Antibody
Wolfgang G. Dippold, Reinhard Klingel, Helga Bernhard, et al.
Cancer Res 1987;47:2092-2097.
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