DISTRIBUTION OF TYPE-VII COLLAGEN IN XENOGRAFTED HUMAN CARCINOMAS

The distribution of type-VII collagen, the main molecular component of the anchoring fibrils (AF) attaching the basal lamina (BL, lamina den sa of the basement membrane) to the surrounding connective tissue, was investigated in four xenografted human carcinomas of the hypopharynx (H-Stg 1), the lung (L 261), the sigmoid colon (CA 1), and the rectum (R 85). The studies were performed with a recently prepared, affinity- purified and highly specific antibody to type-VII collagen by using th e indirect immunofluorescence and the APAAP (alkaline phosphatase anti -alkaline phosphatase) techniques. For comparison, the localization of the intrinsic BL components laminin and type-IV collagen were additio nally analyzed in all four carcinomas. It was shown that type-VII coll agen usually colocalized to laminin and type-IV collagen and was depos ited at the borderline between carcinoma cell clusters and the surroun ding strands of connective tissue in a similar, but more diffuse and l ess continuous distribution than both intrinsic BL components. In the squamous cell carcinoma H-Stg 1 and the adenocarcinoma L 261, type-VII collagen was additionally accumulated in enlarged extracellular space s between carcinoma cells, away from the contact zone to the connectiv e tissue and again colocalized to laminin and type-IV collagen. Numero us carcinoma cells of both xenografts showed remarkable intracytoplasm ic immunoreactivity for the antibody to type-VII collagen. Even in the case of the gastrointestinal carcinomas CA 1 and R 85, faint immunore activity for type-VII collagen was found at the contact zone between t he mucosal epithelium and the surrounding connective tissue. These res ults confirm that epithelial carcinoma cells are obviously involved wi th the synthesis of the main molecular component of AF usually attachi ng the BL to the adjacent connective tissue and hint at a possible cor relation between the localization of type-VII collagen and the observe d pattern of the BL. However, it cannot be decided whether there is a direct causal relation between both phenomena or whether they are both the consequence of an independent but common cause, such as abnormal cellular differentiation of carcinoma cells. In no case, can the disco ntinuities in the distribution of type-VII collagen be explained by ac tive tumor cell invasion since xenografted human carcinomas neither in vade nor metastasize.