Royce L S, Martin G R, Kleinman H K
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Invasion Metastasis. 1992;12(3-4):149-55.
K-1735 clones 10 and M2 are cell lines cloned from a UV-induced murine melanoma. While both lines are highly tumorigenic, only the M2 cells are highly invasive in vitro and metastatic in vivo. Here we have exposed the clone 10 cells to the synthetic peptide PA22-2, which contains the IKVAV sequence from the A chain of laminin and which, like laminin, induces collagenase IV production and enhances metastasis formation by B16F10 cells. Zymogram analysis of conditioned media from clone 10 cells cultured on the peptide demonstrated a dose-dependent increase in collagenase IV activity. When clone 10 cells were cultured on a reconstituted basement membrane (Matrigel), this peptide caused an invasive phenotype comparable to the M2 cells. The invasive clone 10 cells were, however, unable to form lung colonies in vivo in the presence of this peptide. We conclude that this peptide represents an active site on laminin which is able to stimulate the invasiveness of this tumor cell line, but that this activity is not sufficient to confer metastatic potential.
K - 1735克隆株10和M2是从紫外线诱导的小鼠黑色素瘤中克隆得到的细胞系。虽然这两个细胞系都具有高度致瘤性,但只有M2细胞在体外具有高度侵袭性且在体内具有转移性。在此,我们将克隆株10细胞暴露于合成肽PA22 - 2,该肽包含来自层粘连蛋白A链的IKVAV序列,并且与层粘连蛋白一样,可诱导IV型胶原酶的产生并增强B16F10细胞的转移形成。对在该肽上培养的克隆株10细胞的条件培养基进行的酶谱分析表明,IV型胶原酶活性呈剂量依赖性增加。当克隆株10细胞在重组基底膜(基质胶)上培养时,该肽会导致其出现与M2细胞相当的侵袭表型。然而,在存在该肽的情况下,侵袭性克隆株10细胞在体内无法形成肺集落。我们得出结论,该肽代表层粘连蛋白上的一个活性位点,它能够刺激该肿瘤细胞系的侵袭性,但这种活性不足以赋予其转移潜能。