Importance of MUC1 and spontaneous mouse tumor models for understanding the immunobiology of human adenocarcinomas

Abstract

Many important aspects of cancer biology, such as cancer initiation, progression, and metastasis, have been studied in animal models, mostly mice. As long as cancer was considered primarily a genetic disease, the study of transplantable mouse tumors, or even human tumor xenografts in immunocompromised mice, appeared to suffice. Many important genetic events that lead to transformation and in vivo tumor growth were elucidated. However, many even more important factors that determine whether or not the genetic potential of a tumor cell will be realized, such as the host response to the tumor and the tumor microenvironment that influences this response over a long period of time of tumor development, remained untested and unappreciated. This is slowly changing with the advent of molecular techniques that have spurred efforts to engineer better mouse models of human tumors. In this review, we show results of our efforts to combine a genetic mouse model of spontaneous human adenocarcinomas based on a Kras mutation, with an important human molecule MUC1 that is abnormally expressed on human adenocarcinomas, promoting oncogenesis, proinflammatory tumor microenvironment, and immunosurveillance.

MUC1 and metastatic cancer

“…The addition of transgenic Muc1 (KC-Muc1) induced the formation of twice as many premalignant and malignant masses, and Muc1 positive mouse tumors exhibited many more infiltrating cells. 50 Orthotopic models of cancer have also been evaluated for a role of MUC1 in driving metastatic progression. In a model for breast cancer metastasis to the brain, MUC1-expressing bone marrow cells (MA11 cells) were injected into the left ventricle heart chamber of athymic nude mice.…”

Endometriosis, Leiomyoma and Adenomyosis: the Risk of Gynecologic Malignancy

“…MUC1 is a member of the mucin family of molecules and expressed as a type 1transmembrane heterodimer (Finn et al, 2011). It is overexpressed on the majority of adenocarcinomas of the ovary, uterus, breast, pancreas, lung, colon, stomach and prostate, promoting oncogenesis, proinflammatory tumor microenvironment and immunosurveillance (Finn et al, 2011).…”

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

“…Based on this criterion, HMOX1, OSGIN1, DUSP1, and ARRDC3 genes were selected for validation. We included an additional gene, MUC1, that showed different expression pattern in both cell lines and whose expression is associated with poor prognosis in colon cancer (Finn et al 2011). In this study, GAPDH gene and other three reference genes (IPO8, PPIA, and B2M), that have been reported to provide good normalization of RT-qPCR data in colon cancer studies (Sorby et al 2010), were used for data normalization of selected genes.…”