Ford H L, Salim M M, Chakravarty R, Aluiddin V, Zain S B
Department of Biochemistry, University of Rochester School of Medicine, New York 14642, USA.
Oncogene. 1995 Nov 16;11(10):2067-75.
The mts1 gene codes for a 101 amino acid protein belonging to the S100 subfamily of Ca(2+)-binding proteins. Mts1 is overexpressed in metastatic cancers as compared to their nonmetastatic counterparts, and although mts1 is known to be involved in the metastatic phenotype (Davies et al., 1993; Grigorian et al., 1993), the role mts1 plays in this process is not clearly understood. In order to determine what role mts1 plays in the process of metastasis, we have performed transfection studies on nonmetastatic and metastatic mouse mammary adenocarcinoma cell lines, CSML0 and CSML100, respectively (Senin et al., 1983, 1984). The metastatic variant, CSML100, expresses high levels of mts1, whereas the nonmetastatic variant, CSML0, expresses almost no mts1. CSML0 cells transfected with mts1 were assessed in in vitro motility and invasion assays, as well as in vivo metastasis assays to determine the role of mts1 in these processes. Cell lines expressing mts1 display an altered morphology as well as increased motility in modified Boyden chemotaxis chambers. However, no significant increase in in vitro invasion or in in vivo metastasis was observed. Therefore, the presence of mts1 may be important for metastasis by increasing motility, but may not be sufficient for invasion in vitro or metastasis in vivo. Very low levels of type IV collagenase activities were observed in CSML0 cells and the transfectants, as opposed to the highly metastatic CSML100 cells, where high levels of type IV collagenase activities were observed. It is possible that the presence of these proteases in addition to mts1 may be responsible for the high metastatic potential of the CSML100 in vivo.
mts1基因编码一种由101个氨基酸组成的蛋白质，该蛋白质属于Ca(2+)结合蛋白的S100亚家族。与非转移性癌症相比，mts1在转移性癌症中过度表达，尽管已知mts1参与转移表型（戴维斯等人，1993年；格里戈里安等人，1993年），但mts1在这一过程中所起的作用尚不清楚。为了确定mts1在转移过程中所起的作用，我们分别对非转移性和转移性小鼠乳腺腺癌细胞系CSML0和CSML100进行了转染研究（塞宁等人，1983年、1984年）。转移性变体CSML100表达高水平的mts1，而非转移性变体CSML0几乎不表达mts1。对转染了mts1的CSML0细胞进行了体外运动和侵袭试验以及体内转移试验，以确定mts1在这些过程中的作用。表达mts1的细胞系在改良的博伊登趋化小室中显示出形态改变以及运动性增加。然而，未观察到体外侵袭或体内转移有显著增加。因此，mts1的存在可能通过增加运动性对转移很重要，但可能不足以促进体外侵袭或体内转移。与高度转移性的CSML100细胞（观察到高水平的IV型胶原酶活性）相反，在CSML0细胞和转染细胞中观察到非常低水平的IV型胶原酶活性。除mts1外，这些蛋白酶的存在可能是CSML100在体内具有高转移潜能的原因。
