Expression of type IV collagen α1(IV)-α6(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 α1(IV)-α6(IV) chains. Chains α1,2(IV) are widely expressed in BMs while α3(IV)-α6(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. α1,2(IV) chains were found in all BMs of fetal and adult kidney as well as of renal tumors, while α3(IV)- α6(IV) chains were found in BMs of distal segments of developing and mature tubules. α3(IV)-α5(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 α3(IV)-α6(IV) with papillary variants showing only expression of α5(IV) chain. There was a distinct expression of α3(IV)-α5(IV) chains in BMs of 3 oncocytomas. In 2 of them a variable expression of the α6(IV) chain was seen. In 3 of 4 xenografts, immunoreactivity for human-specific monoclonal antibody (MAb) for α1,2(IV) was seen in the BM-like structures. No α3-α6(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 α3(IV)-α6(IV) chains. In experimental xenograft tumors, both implanted RCC cells and host stromal cells have a capacity to produce type IV collagen.