Gouon V, Tucker G C, Kraus-Berthier L, Atassi G, Kieffer N
Laboratoire Franco-Luxembourgeois de Recherche Biomédicale, Centre Universitaire, Luxembourg.
Int J Cancer. 1996 Nov 27;68(5):650-62. doi: 10.1002/(SICI)1097-0215(19961127)68:5<650::AID-IJC16>3.0.CO;2-5.
In situ changes in the repertoire of integrins and proteolytic enzymes have been demonstrated during melanoma metastasis. To investigate whether established human melanoma cell lines, injected into nude mice, could undergo phenotypic changes similar to those observed in in situ lesions, we studied 3 melanoma cell lines of distinct metastatic origin, adherent HT-144 and SK-MEL-2 cells, and non-adherent SK-MEL-1 cells for integrin expression, proteolytic enzyme repertoire and invasive potential after in vitro culture. Heterogeneity in integrin expression, such as elevated levels in alpha(v)beta3 in SK-MEL-1 and SK-MEL-2 cells and low expression in HT-144 cells, correlated with their in vitro invasiveness, since only the adherent HT-144 and SK-MEL-2 cells were able to invade Matrigel, and in addition, secreted a 72-kDa gelatinase. In contrast, no similar correlation could be established in nude mice, as all 3 cell lines, including the non-adherent SK-MEL-1 cells, were tumorigenic when injected s.c., while only HT-144 consistently produced experimental lung metastasis. Immunochemical analysis of the integrin profile in s.c. xenografts revealed over-expression of alpha(v), beta1 and beta3 integrins exclusively in HT-144 cells, as well as increased expression of beta3 in HT-144 cell lung metastases, as confirmed by PCR analysis using species-specific primers, while zymography and Western-blot analysis demonstrated de novo expression of the 92-kDa gelatinase MMP-9 in HT-144 xenografts. Our results highlight a positive correlation between up-regulated beta3 integrin and MMP-9 expression in human HT-144 melanoma cell tumors grown in nude mice.
在黑色素瘤转移过程中，整合素和蛋白水解酶的原位变化已得到证实。为了研究注入裸鼠体内的已建立的人黑色素瘤细胞系是否会发生类似于原位病变中观察到的表型变化，我们研究了3种具有不同转移起源的黑色素瘤细胞系，贴壁的HT-144和SK-MEL-2细胞，以及非贴壁的SK-MEL-1细胞，检测其体外培养后的整合素表达、蛋白水解酶谱和侵袭潜能。整合素表达的异质性，如SK-MEL-1和SK-MEL-2细胞中α(v)β3水平升高而HT-144细胞中表达较低，与它们的体外侵袭性相关，因为只有贴壁的HT-144和SK-MEL-2细胞能够侵袭基质胶，此外，它们还分泌一种72-kDa的明胶酶。相比之下，在裸鼠中未能建立类似的相关性，因为所有3种细胞系，包括非贴壁的SK-MEL-1细胞，皮下注射时都具有致瘤性，而只有HT-144始终能产生实验性肺转移。对皮下异种移植物中整合素谱的免疫化学分析显示，仅在HT-144细胞中α(v)、β1和β3整合素过表达，并且通过使用物种特异性引物的PCR分析证实，HT-144细胞肺转移中β3表达增加，而酶谱分析和蛋白质印迹分析表明，HT-144异种移植物中92-kDa的明胶酶MMP-9从头表达。我们的结果突出了在裸鼠中生长的人HT-144黑色素瘤细胞肿瘤中上调的β3整合素与MMP-9表达之间的正相关。
