The Molecular Mechanism Underlying Modulation Of The Metastatic Potential Of Murine Mammary Adenocarcinoma Cell Line MA891 By IFN-γ

Invasion and metastasis are the most common and fundamental characteristics of malignancies. In large number of patients with cancer, metastasis may well have occurred at the time of diagnosis. Although significant improvements have been made in early diagnosis, surgical techniques, general patient care, and local and systemic adjuvant therapies, modern medicine can do little to cure metastasis because they are resistant to convnetional therapies. There comes the urgent need to study and understand the exact mechanisms underlying tumor metastasis in order to design more effective therapy for cancer.Metastasis is an extremely complicated process which consists of many sequential interrelated steps. The transformed cells must grow progressively at the primary tumor site, induce neovascularization, intravasate into blood or lymphatic vessles, survive from the host immune and non-immune clearance as well as the turbulence of the blood flow, arrest in the capillary beds of the proper organs, extravasate and proliferate within the organ parenchyma to form metastasis. A failure at any of the steps aborts the process. Metastasis is the ultimate result of both the alteration of the genes in the tumor cells and imbalance between positive and negative regulations. Active research has been lunched to identify the genetic control of the metastatic phenotype and/or genes responsible for regulating discrete steps of the metastatic process.We previously observed that pretreatment of MA891, a cell line from a spontaneous mouse mammary adenocarcinoma with two different interferons exerted totally different effects on its metastatic potential. EFN-α inhibited, while DFN-γ increased lung colonization when MA891 cells were injected s.c. and i.v. into the syngenic TA II mice. The different effects might be due to the induction of specific gene expression within the cell. We compared the differences at mRNA level between the cells treated with IFN-α and IFN-γ using mRNA differential display technique and isolated four differentially...