Nakano S, Iyama K, Ogawa M, Yoshioka H, Sado Y, Oohashi T, Ninomiya Y
Department of Surgical Pathology, Kumamoto University School of Medicine, Japan.
Lab Invest. 1999 Mar;79(3):281-92.
Type IV collagen, the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. We investigated the cellular regulation and origin of these alpha(IV) chains in normal and neoplastic breast tissues by immunohistochemistry by using alpha(IV) chain-specific antibodies and by in situ hybridization. In normal breast, alpha1(IV) and alpha2(IV) chains were stained in all BM, whereas alpha5(IV) and alpha6(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, alpha1(IV) and alpha2(1V) chains were discontinuously or negatively stained in the cancer cell nests, and the assembly of alpha5(IV) and alpha6(IV) chains into the BM was completely inhibited. Coexpression of alpha5(IV) and alpha6(IV) chains was related to the localization of alpha-smooth muscle actin (alpha-SMA)-positive myoepithelial cells. By in situ hybridization, in fibroadenoma and invasive ductal carcinoma, the signals for alpha1(IV) and alpha2(IV) mRNA were abundant in stromal cells. However, the signals for alpha5(IV) and alpha6(IV) mRNA were not seen in any of these cells. In contrast, in intraductal papilloma, coexpression of alpha1 (IV)/alpha2(IV) mRNA and alpha5(IV)/alpha6(IV) mRNA was identified in epithelial cells. The results indicate that the mammary gland forms a second network of BM composed of alpha5(IV)/alpha6(IV) chains, in addition to the classic network of alpha1(IV)/alpha2(IV) chains. The expression of type IV collagen alpha chains seems to be differentially regulated by the epithelial-myoepithelial interaction and to be associated with the invasive potential of breast cancer.
IV型胶原是基底膜（BM）的主要成分，由六条基因不同的α链组成。我们通过免疫组织化学方法，使用α（IV）链特异性抗体并结合原位杂交技术，研究了正常和肿瘤性乳腺组织中这些α（IV）链的细胞调控及来源。在正常乳腺中，α1（IV）和α2（IV）链在所有基底膜中均有染色，而α5（IV）和α6（IV）链则以线性模式局限于乳腺基底膜中。在良性乳腺肿瘤和浸润性导管癌的导管内成分中观察到了类似的免疫染色模式。然而，在浸润性导管癌中，α1（IV）和α2（IV）链在癌细胞巢中呈间断性或阴性染色，并且α5（IV）和α6（IV）链组装到基底膜的过程被完全抑制。α5（IV）和α6（IV）链的共表达与α-平滑肌肌动蛋白（α-SMA）阳性肌上皮细胞的定位有关。通过原位杂交发现，在纤维腺瘤和浸润性导管癌中，α1（IV）和α2（IV）mRNA信号在基质细胞中丰富。然而，在这些细胞中均未检测到α5（IV）和α6（IV）mRNA信号。相反，在导管内乳头状瘤中，上皮细胞中鉴定出α1（IV）/α2（IV）mRNA和α5（IV）/α6（IV）mRNA的共表达。结果表明，除了经典的α1（IV）/α2（IV）链网络外，乳腺还形成了由α5（IV）/α6（IV）链组成的第二个基底膜网络。IV型胶原α链的表达似乎受上皮-肌上皮相互作用的差异调节，并与乳腺癌的侵袭潜能相关。
