Abstract
Studies have indicated that the aggregation of activated platelets with cancer cells facilitates tumor metastasis; the adhesion molecule P-selectin may be an important mediator of this process, but the detailed mechanism is unclear. In the current study, we established a B16F10 (B16) cell metastatic model in P-selectin knockout (P-sel−/−) mice to determine the effect of P-selectin-mediated platelet adhesion on metastasis. Compared with C57 mice, P-sel−/− mice developed fewer metastatic foci, and cell proliferation within the metastatic tumors was inhibited by P-selectin deficiency. The platelet refusion assay demonstrated that mice with P-sel−/− platelets developed fewer lung metastatic foci (P<0.01) with a lower microvascular density (MVD) than mice with wild-type platelets. A co-culture model of platelets and B16 cells was utilized to determine the difference in VEGF concentration in the supernatants. The results demonstrated that the supernatant from the P-sel−/− platelet/B16 co-culture had a lower concentration of VEGF. Therefore, our findings indicated that P-selectin deficiency inhibited the metastasis of B16 cells and that wild-type platelet refusion reversed this inhibition. The P-selectin-mediated interaction between platelets and B16 cells promoted angiogenesis by up-regulating VEGF.
Highlights
Cutaneous melanin pigment, which is synthesized from Ltyrosine and L-DOPA and excreted by melanocytes, plays an important role in camouflage and protection against solar radiation [1]
Hematogenous metastasis is a highly coordinated, sequential, dynamic, multistep process in which cancer cells interact with a variety of host cells
Most of the circulating tumor cells (CTCs) are damaged during circulatory transport
Summary
Cutaneous melanin pigment, which is synthesized from Ltyrosine and L-DOPA and excreted by melanocytes, plays an important role in camouflage and protection against solar radiation [1]. In response to multiple agents, melanocytes can become cancerous, resulting in the development of malignant melanoma. Melanogenesis can affect the behavior of melanoma cells [2]. Melanoma has become increasingly common, and its associated mortality rate is high. The prognosis for melanoma patients with distant metastases is especially poor, with a median survival time of only 8 months [3]. Melanoma cells tend to metastasize during early stages of tumorigenesis, largely because of their highly metastatic nature. The tumor becomes resistant to most therapies, including chemotherapy, radiotherapy, and immunotherapy [4]
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