Luparello C, Sheterline P, Pucci-Minafra I, Minafra S
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Italy.
J Cell Sci. 1991 Sep;100 ( Pt 1):179-85. doi: 10.1242/jcs.100.1.179.
Ductal infiltrating carcinoma (d.i.c.) of human breast is a highly invasive neoplasm characterized by enhanced deposition of collagen. Paradoxically, enhanced collagen deposition is not correlated with inhibition of the migration of tumour cells into the host tissue. d.i.c. is characterized by the reappearance of 'embryonic' type I-trimer collagen and an increase in type V collagen content in the matrix. The effects of these two collagen types were compared with type I collagen as culture substrata on the spreading pattern, cytoskeletal organization and motile behaviour of 8701-BC breast carcinoma cells using rhodamine-phalloidin staining, a DNAase I-competition assay, scanning electron microscopy and time-lapse video-microscopy. Cells grown on type I collagen were stationary, showing a well-spread morphology and an extensive stress fibre pattern. Cells grown on type V collagen were also stationary, but displayed a poorly spread and elongated morphology. In contrast, cells grown on trimer collagen were motile and displayed a compact morphology and a reduced content of stress fibres. Both single-cell and group motility were detectable on trimer collagen substratum. These data are consistent with the existence of two opposite local signals, type I-trimer and type V collagens, which may confer a more or a less metastatic phenotype on breast carcinoma cells. Moreover, the synthesis of trimer collagen in d.i.c. is conceivably instrumental in providing new stromal pathways permitting tumour cells to infiltrate the host tissue.
人乳腺导管浸润癌(DIC)是一种具有高度侵袭性的肿瘤,其特征在于胶原蛋白沉积增加。矛盾的是,胶原蛋白沉积增加与肿瘤细胞向宿主组织迁移的抑制并无关联。DIC的特征是“胚胎型”I型三聚体胶原蛋白重新出现以及基质中V型胶原蛋白含量增加。使用罗丹明 - 鬼笔环肽染色、DNA酶I竞争试验、扫描电子显微镜和延时视频显微镜,将这两种胶原蛋白类型与I型胶原蛋白作为培养底物对8701 - BC乳腺癌细胞的铺展模式、细胞骨架组织和运动行为的影响进行了比较。在I型胶原蛋白上生长的细胞静止不动,呈现出良好铺展的形态和广泛的应力纤维模式。在V型胶原蛋白上生长的细胞同样静止不动,但呈现出铺展不佳且细长的形态。相比之下,在三聚体胶原蛋白上生长的细胞具有运动性,呈现出紧凑的形态且应力纤维含量减少。在三聚体胶原蛋白底物上可检测到单细胞和群体运动。这些数据与两种相反的局部信号,即I型三聚体和V型胶原蛋白的存在相一致,它们可能赋予乳腺癌细胞或多或少的转移表型。此外,DIC中三聚体胶原蛋白的合成可以想象有助于提供新的基质途径,使肿瘤细胞能够浸润宿主组织。