Objective: Mouse mammary cancer cell line MCH66 shows invasion-independent metastasis. To elucidate this metastatic mechanism, the biological characteristics putatively related to metastasis were analyzed using several cell lines with different metastatic abilities derived from MCH66.
Methods: Metastatic capacity, invasive activity, growth property, and mRNA expressions of factors associated with endothelial cell proliferation were comparatively analyzed in MCH66 and its sublines.
Results: Lu10 subline exhibited higher metastatic potential to the lungs and lymph nodes (100%) than MCH66 or Lu1 subline (0/5, 0/5 each). The growth rate was almost identical between Lu10 and MCH66, and Lu10 revealed weaker invasive activity in vitro than MCH66. In Lu10 tumors in mice, well-developed sinusoidal blood vessels and dilated lymphatics were noted compared with in Lu1 tumors. Accordingly, Lu10 showed higher expression of vascular endothelial growth factor (VEGF)-C, -D, platelet-derived growth factor (PDGF)-B and pleiotrophin than Lu1, while the expression of other growth factors such as VEGF-A, midkine, angiogenin, hepatocyte growth factor, PDGF-A, and basic fibroblast growth factor remained unchanged between Lu1 and Lu10.
Conclusion: These data indicate that high invasiveness and rapid growth are not required for this metastatic process, and some angiogenic mediators are involved in blood-borne and lymphatic metastasis.