Basal cell carcinomas grown in nude mice produce and deposit fibronectin in the extracellular matrix.
Epidermal cells in vitro produce and deposit fibronectin (FN) in the pericellular matrix. Such FN production by epidermal cells may be involved in vivo in wound reepithelialization, tissue morphogenesis, and growth of epithelial tumors. The purpose of this study was to examine whether the FN, previously shown to be within and surrounding human basal cell carcinoma (BCC) lobules, was in part the product of epidermal-derived tumor cells. To examine this question we took advantage of our ability to grow human BCC in nude mice. Since we could demonstrate that all stromal cells surrounding the BCC were of mouse origin, antibodies specific for human FN would distinguish epithelial-derived FN from mesenchymal-derived FN. Five solid BCCs were implanted subcutaneously in nude mice. Growing tumors were removed after 60 days, snap-frozen, sectioned on a cryostat, and verified microscopically as BCC. The Hoescht DNA stain, which can distinguish mouse and human nuclei, demonstrated that mouse, not human, fibroblasts occupied the stroma surrounding each tumor lobule. Sections of all 5 BCCs were stained by immunofluorescence and immunoperoxidase techniques with antibodies to bullous pemphigoid (BP) antigen, laminin (LM), and FN. BP antigen and LM were present at the basement membrane zone (BMZ) of all tumor lobules as previously described for in situ BCC. FN staining was present along the BMZ, within the tumor lobules, and in the surrounding stroma. Antibodies to human FN were passed over a mouse FN affinity column to absorb antibodies which cross-reacted with mouse FN. The resultant antibody preparation, which was specific for human FN in this system, continued to demonstrate FN along the BMZ and within the tumors, but failed to stain FN in more distant stroma. Epidermal-derived cells, therefore, can synthesize and deposit FN in vivo in adjacent extracellular matrix. We speculate that this FN matrix may facilitate growth of BCC in this model.
D000818:Animals; D000918:Antibody Specificity; D001324:Autoantigens / Q000032:analysis; D001485:Basement Membrane / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D004247:DNA / Q000032:analysis; D000071821:Dystonin; D004817:Epidermis / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000032:analysis; D005353:Fibronectins / Q000096:biosynthesis / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007797:Laminin / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D004247:DNA; D000071821:Dystonin; D005353:Fibronectins; D007797:Laminin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human; C095667:Dst protein, mouse