Expression of type IV collagen alpha1(IV)-alpha6(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 (BMs). It is composed of polypeptides named alpha1(IV)-alpha6(IV) chains. Chains alpha1,2(IV) are widely expressed in BMs while alpha3(IV)-alpha6(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 carcinomas (RCCs) and their metastases and in experimental xenografts of human tumors. alpha1,2(IV) chains were found in all BMs of fetal and adult kidney as well as of renal tumors, while alpha3(IV)-alpha6(IV) chains were found in BMs of distal segments of developing and mature tubules. alpha3(IV)-alpha5(IV) chains were seen also in BMs of developing fetal glomeruli after the capillary loop stage. Most of the RCCs and their metastases showed occasional expression of alpha3(IV)-alpha6(IV) with papillary variants showing only expression of alpha5(IV) chain. There was a distinct expression of alpha3(IV)-alpha5(IV) chains in BMs of 3 oncocytomas. In 2 of them a variable expression of the alpha6(IV) chain was seen. In 3 of 4 xenografts, immunoreactivity for human-specific monoclonal antibody (MAb) for alpha1,2(IV) was seen in the BM-like structures. No alpha3-alpha6(IV) was seen in any of the xenografts, while polyclonal antiserum for type IV collagen presented immunoreactivity in BMs of all xenografts. Our results show that oncocytomas and most of the RCCs express scarce variants of type IV collagen containing alpha3(IV)-alpha6(IV) chains. In experimental xenograft tumors, both implanted RCC cells and host stromal cells have a capacity to produce type IV collagen.