Wach F, Eyrich A M, Wustrow T, Krieg T, Hein R
Department of Dermatology, University of Regensburg, Germany.
J Dermatol Sci. 1996 Jun;12(2):118-26. doi: 10.1016/0923-1811(95)00470-x.
Tumor invasion of basement membranes is a complex multi-step process. Altered adhesion, as well as increased cell locomotion contribute to tumor cell invasion and metastasis. A variety of in vitro models have been used to measure cell invasiveness. The invasion of basement membranes can be simulated in vitro in blind well Boyden Chambers using the reconstituted basement membrane matrigel or collagen type I as the invasion barrier. The aim of our study was to compare the migration and invasive capacity of epidermal tumor cells (TR 131, TR 146, SCL II, FaDu, HLaC 79) and melanoma cells derived from primary tumors (Mel Ei, Mel Ho, Mel Juso, Mel Wei) or their metastases (Mel Ju, Mel Im, Sk Mel 1, Sk Mel 28). Chemotactic response of epidermal tumor cells was increased toward fibroblast conditioned medium and fibronectin (20 micrograms/ml), while laminin (100 micrograms/ml) stimulated chemotaxis in only 3 epidermal tumor cell lines (HLaC 79, FaDu, TR 146), EGF (10 ng/ml) in only 4 cases (SCL II, FaDu, TR 131, TR 146), and interleukin-1 (IL-1) in only 1 case (FaDu). Epithelial tumor cell conditioned medium had no chemotactic influence on epithelial tumor cells. Fibroblast conditioned medium, fibronectin, EGF and PDGF were potent chemoattractants for all melanoma tumor cells, whereas IL-1 did not induce a significant chemotactic response. While two epithelial tumor cell lines (FaDu, TR 146) were able to penetrate collagen type I, matrigel was an impenetrable barrier for all epithelial tumor cells. Two cell lines from melanoma primary tumors (Mel Ho, Mel Ei) and two cell lines from melanoma metastases (Sk Mel 1, Sk Mel 28) showed no invasion through collagen type I and matrigel, whereas invasion through both barriers could be observed for the metastatic cell lines Mel Ju and Mel Im and in the primary tumor cell line Mel Wei. Therefore, the clinical observation of late and rare metastasis in epithelial tumors and early metastasis in melanoma correlate with our in vitro investigation of invasive behavior in tumor cells. No significant correlation between the invasiveness of melanoma cell lines and their clinical origin could be demonstrated suggesting the existence of subpopulations with varying invasive potential.
肿瘤侵袭基底膜是一个复杂的多步骤过程。黏附改变以及细胞运动增加均有助于肿瘤细胞的侵袭和转移。已使用多种体外模型来测量细胞侵袭性。使用重组基底膜基质胶或I型胶原作为侵袭屏障，可在盲孔Boyden小室中体外模拟基底膜的侵袭。我们研究的目的是比较表皮肿瘤细胞（TR 131、TR 146、SCL II、FaDu、HLaC 79）以及源自原发性肿瘤（Mel Ei、Mel Ho、Mel Juso、Mel Wei）或其转移灶（Mel Ju、Mel Im、Sk Mel 1、Sk Mel 28）的黑色素瘤细胞的迁移和侵袭能力。表皮肿瘤细胞对成纤维细胞条件培养基和纤连蛋白（20微克/毫升）的趋化反应增强，而层粘连蛋白（100微克/毫升）仅刺激3种表皮肿瘤细胞系（HLaC 79、FaDu、TR 146）的趋化性，表皮生长因子（EGF，10纳克/毫升）仅在4种情况（SCL II、FaDu、TR 131、TR 146）下有刺激作用，白细胞介素-1（IL-1）仅在1种情况（FaDu）下有刺激作用。上皮肿瘤细胞条件培养基对上皮肿瘤细胞没有趋化影响。成纤维细胞条件培养基、纤连蛋白、EGF和血小板衍生生长因子（PDGF）对所有黑色素瘤肿瘤细胞都是有效的化学引诱剂，而IL-1未诱导出明显的趋化反应。虽然两种上皮肿瘤细胞系（FaDu、TR 146）能够穿透I型胶原，但基质胶对所有上皮肿瘤细胞都是不可穿透的屏障。来自黑色素瘤原发性肿瘤的两种细胞系（Mel Ho、Mel Ei）和来自黑色素瘤转移灶的两种细胞系（Sk Mel 1、Sk Mel 28）未显示出穿过I型胶原和基质胶的侵袭，而转移细胞系Mel Ju和Mel Im以及原发性肿瘤细胞系Mel Wei可观察到穿过这两种屏障的侵袭。因此，上皮肿瘤中晚期和少见转移以及黑色素瘤中早期转移的临床观察结果与我们对肿瘤细胞侵袭行为的体外研究相关。黑色素瘤细胞系的侵袭性与其临床来源之间未显示出显著相关性，这表明存在具有不同侵袭潜能的亚群。
