The roles of plasma proteins and neutrophils in melanoma metastasis

Open Access
Godiska, Lisa Marie
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Cheng Dong, Thesis Supervisor
  • William O Hancock, Honors Advisor
  • Margaret June Slattery, Faculty Reader
  • melanoma
  • metastasis
  • plasma proteins
  • neutrophils
The metastatic behavior of melanoma cells was studied both in vitro and in vivo to ascertain the roles of thrombin, fibrin and polymorphonuclear neutrophils, PMNs, in mediating melanoma metastasis. Previous experimental studies have shown that thrombin production further increases in the tumor microenvironment, which promotes the conversion of fibrinogen to fibrin that in turn, facilitates tumor metastasis. The present in vitro studies support the hypothesis that thrombin increases in melanoma co-cultures in the presence of human plasma compared to the normal cases. The increased production of thrombin further promotes the conversion of fibrinogen to fibrin. Fibrin was then found to promote the aggregation of PMNs to tumor cells. This aggregation supports the hypothesis that fibrin mediates melanoma metastasis and gives mechanistic details on how this mediation occurs. In vivo research from this study developed a preliminary mouse model to be used in Dr. Cheng Dong’s laboratory to study and quantify melanoma metastasis in black six mice. Using this model the role of PMNs in mediating melanoma metastasis will be studied. Further work in vivo with the control mouse model that was developed in this study could support the in vitro hypothesis that PMNs facilitate melanoma metastasis due to the increased aggregation of PMNs to tumor cells by fibrin.