EXPRESSION OF TYPE-IV COLLAGEN ALPHA-1(IV)-ALPHA-6(IV) POLYPEPTIDES IN NORMAL AND DEVELOPING HUMAN KIDNEY AND IN RENAL-CELL CARCINOMAS AND ONCOCYTOMAS

Type IV collagen trimer is a major component of basement membranes (BM s). It is composed of polypeptides named alpha 1(IV)-alpha 6(1V) chain s. Chains alpha 1,2(IV) are widely expressed in BMs while alpha 3(IV)- alpha 6(IV) are more restricted in human tissues. We have now studied by immunohistochemical means the distribution of collagen IV chains in fetal and adult human kidney, in oncocytomas, in renal cell carcinoma s (RCCs) and their metastases and in experimental xenografts of human tumors. alpha 1,2(IV) chains were found in all BMs of fetal and adult kidney as well as of renal tumors, while alpha 3(IV)-alpha 6(IV) chain s were found in BMs of distal segments of developing and mature tubule s. alpha 3(IV)-alpha 5(IV) chains were seen also in BMs of developing fetal glomeruli after the capillary loop stage. Most of the RCCs and t heir metastases showed occasional expression of alpha 3(IV)-alpha 6(IV ) with papillary variants showing only expression of alpha 5(IV) chain . There was a distinct expression of alpha 3(IV)-alpha 5(IV) chains in BMs of 3 oncocytomas. In 2 of them a variable expression of the alpha 6(IV) chain was seen. In 3 of 4 xenografts, immunoreactivity for huma n-specific monoclonal antibody (MAb) for alpha 1,2(IV) was seen in the BM-like structures. No alpha 3-alpha 6(IV) was seen in any of the xen ografts, while polyclonal antiserum for type IV collagen presented imm unoreactivity in BMs of all xenografts. Our results show that oncocyto mas and most of the RCCs express scarce variants of type IV collagen c ontaining alpha 3(IV)-alpha 6(IV) chains. In experimental xenograft tu mors, both implanted RCC cells and host stromal cells have a capacity to produce type IV collagen. (C) 1997 Wiley-Liss, Inc.