Proteomic assessment of human ovarian cancer cell lines xenotransplanted into the hamster cheek pouch

Abstract

Ovarian cancer, commonly arises from the surface epithelium, remains the fifth common cause of cancer death in women and the most lethal of gynecological cancers. One reason for such lethality is that the disease is seldom diagnosed before it progresses to the fully malignant state (invasive and/or metastatic). Secondly, the majority of ovarian cancer patients develop resistance to the current treatment regimens that initially yield very effective regression at both primary and metastatic tumor sites. There is a need for better strategies to: 1) appropriately assess ovarian tumor cell growth and malignant progression (prognosis) and 2) test how they may respond to current and/or new treatment agents (therapeutic assays) AND do that in a whole animal system. Our approach is transplantation of the human tumor cells into an animal host, a procedure known as in vivo xenotransplantation. I tested the feasibility of linking our hamster experimental system to clinical diagnosis and treatment of ovarian cancer. I harvested growing cultures of established human tumor cell lines (donor material), xenotransplanted the cell suspensions into the hamster cheek pouch (an immunologically privileged host site), and then assessed transplant status (general appearance, dimensions, vascularization state, etc.). We harvested and generated formalin-fixed and paraffin-embedded (FFPE) histology specimens of viable xenotransplant masses that were established from two cell lines (SKOV3p43 and A2780p4). Finally, I conducted proteomic assessments using immunoblot analysis of total protein extracts prepared from the cultured cell lines and Immunohistochemical analysis of the xenotransplant mass / FFPE tissue sections. Our results so far provide proof-of principle that the hamster cheek pouch transplantation can be exploited for translational research on ways to improve the clinical diagnosis, prognosis, and treatment of ovarian cancer.