Thomas L, Chan P W, Chang S, Damsky C
Department of Anatomy, School of Dentistry, University of California San Francisco 94143-0512.
J Cell Sci. 1993 May;105 ( Pt 1):191-201. doi: 10.1242/jcs.105.1.191.
Cell interactions with the extracellular matrix play a critical role in regulating complex processes such as terminal differentiation and tumor progression. In these studies we describe a melanoma cell system that should be useful in addressing the regulation of cell-matrix interactions and the roles they play in regulating differentiation and cell invasiveness. CS (suspension)-1 melanoma cells are relatively well differentiated: they are melanotic, responsive to melanocyte-stimulating hormone, and express TA99, a melanosome membrane differentiation marker. Their repertoire of integrin receptors for extracellular matrix ligands is limited; in particular, they lack receptors for vitronectin, accounting for the observation that they are nonadherent when cultured in the presence of serum. CS-1 cells are noninvasive as well, and express low levels of both metalloproteinases and activated plasminogen activators. Treatment of these cells with melanocyte-stimulating hormone causes them to increase melanin production and assume an arborized phenotype, suggesting that it promotes their further differentiation. In contrast, treatment of CS-1 with the thymidine analog 5-bromodeoxyuridine, converts them to a highly invasive cell population (termed BCS-1) that loses its differentiated properties and responsiveness to melanocyte-stimulating hormone, acquires a broad integrin repertoire (including vitronectin receptors), and expresses elevated levels of metalloproteinases and activated urokinase. From these observations and findings of others on BrdU treatment of other developmental lineages, we hypothesize that BrdU both suppresses differentiation and promotes invasiveness of CS-1 cells. The demonstrated manipulability of CS-1 cells should make them extremely useful for studying the regulation of both terminal differentiation and tumor progression in the melanocyte lineage.
细胞与细胞外基质的相互作用在调节诸如终末分化和肿瘤进展等复杂过程中起着关键作用。在这些研究中，我们描述了一种黑色素瘤细胞系统，该系统对于研究细胞 - 基质相互作用的调节及其在调节分化和细胞侵袭性中所起的作用应该是有用的。CS（悬浮）-1黑色素瘤细胞相对分化良好：它们是黑素化的，对促黑素细胞激素有反应，并表达TA99，一种黑素体膜分化标志物。它们针对细胞外基质配体的整合素受体库有限；特别是，它们缺乏玻连蛋白受体，这解释了在血清存在下培养时它们不粘附的现象。CS-1细胞也是非侵袭性的，并且金属蛋白酶和活化的纤溶酶原激活剂的表达水平都很低。用促黑素细胞激素处理这些细胞会导致它们增加黑色素生成并呈现树状表型，这表明它促进了它们的进一步分化。相比之下，用胸苷类似物5-溴脱氧尿苷处理CS-1，会将它们转化为高度侵袭性的细胞群体（称为BCS-1），该群体失去其分化特性和对促黑素细胞激素的反应性，获得广泛的整合素库（包括玻连蛋白受体），并表达升高水平的金属蛋白酶和活化的尿激酶。根据这些观察结果以及其他人关于BrdU对其他发育谱系处理的发现，我们假设BrdU既抑制CS-细胞的分化又促进其侵袭性。已证明的CS-1细胞的可操作性应该使其对于研究黑素细胞谱系中的终末分化和肿瘤进展的调节极为有用。
