Distribution of collagen type IV alpha1-6 chains in human normal colorectum and colorectal cancer demonstrated by immunofluorescence staining using chain-specific epitope-defined monoclonal antibodies.
OBJECTIVE
Loss of basement membrane (BM) components, such as type IV collagen, has been demonstrated in colorectal cancer, but the fine diversity of the assembly of alpha (IV) chains, the composition of type IV collagen, and alterations in the collagen have not been fully analyzed. Here, we defined immunohistochemically the expression of alpha1-6 (IV) chains in colorectal cancer tissues and adjacent normal mucosa by the use of chain-specific monoclonal antibodies.


METHODS
Tissue samples of tumor and adjacent normal mucosa obtained from patients with colorectal adenocarcinoma were stained with chain-specific monoclonal antibodies raised against synthetic peptides of individual alpha (IV) chains using an indirect immunofluorescence method.


RESULTS
In the normal mucosa, alpha1 (IV), alpha2 (IV), alpha5 (IV), and alpha6 (IV) were found in the BM-delineating mucosal epithelium and the gland crypts, whereas alpha3 (IV) and alpha4 (IV) were limited to the BM of the luminal surface epithelium. In contrast, staining of alpha3-6 (IV) was rarely observed in the BM of cancer cells. Staining of alpha1 (IV) and alpha2 (IV) was reduced or lost from the cancer BM in relation to the degree of tumor differentiation: continuous staining in well-differentiated portions, discontinuous staining in moderately differentiated portions, and absence of staining in poorly differentiated portions.


CONCLUSIONS
Our findings indicate that type IV collagen expression is altered in the BM of colorectal cancer as a result of changes of alpha (IV) chain expression, particularly alpha1 (IV) and alpha2 (IV), in relation to the degree of tumor differentiation.
Oka
Yuko
Y
Department of Internal Medicine, Shigei Medical Research Institute and Hospital, Okayama, Japan.
Naito
Ichiro
I
Manabe
Koji
K
Sado
Yoshikazu
Y
Matsushima
Hiroshi
H
Ninomiya
Yoshifumi
Y
Mizuno
Motowo
M
Tsuji
Takao
T
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D024141:Collagen Type IV