Differential tissular expression and localization of type IV collagen α1(IV), α2(IV), α5(IV), and α6(IV) chains and their mRNA in normal breast and in benign and malignant breast tumors

Type IV collagen, the major component of basement membrane (BM) is composed of six genetically distinct chains. We investigated the cellular regulation and origin of these a(IV) chains in normal and neoplastic breast tissues by immunohistochemistry by using α(IV) chain-specific antibodies and by in situ hybridization. In normal breast α1(IV) and α2(IV) chains were stained in all BM, whereas α5(IV) and ↑(IV) chains were restrictively localized in a linear pattern in the BM of the mammary gland. Similar immunostaining profiles were observed in benign breast tumors and in the intraductal components of invasive ductal carcinoma. However, in invasive ductal carcinoma, α1(IV) and α2(IV) chains were discontinuously or negatively stained in the cancer cell nests, and the assembly of α5(IV) and α6(IV) chains into the BM was completely inhibited. Coexpression of α5(IV) and α6(IV) chains was related to the localization of α-smooth muscle actin (α-SMA)-positive myoepithelial cells. By in situ hybridization, in fibroadenoma and invasive ductal carcinoma, the signals for α1(IV) and c 1/2 (IV) mRNA were abundant in stromal cells. However, the signals for α5(IV) and α6(IV) mRNA were not seen in any of these cells. In contrast, in intraductal papilloma, coexpression of α1(IV)/α2(IV) mRNA and α5(IV)/α6(IV) mRNA was identified in epithelial cells. The results indicate that the mammary gland forms a second network of BM composed of α5(IV)/α6(IV) chains, in addition to the classic network of α1(IV)/α2(IV) chains. The expression of type IV collagen α chains seems to be differentially regulated by the epithelial-myoepithelial interaction and to be associated with the invasive potential of breast cancer.