ABSTRACT
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.
