ABSTRACT
Colorectal cancer (CRC) is a challenging disease, with a high mortality rate and limited effective treatment options, particularly for late-stage disease. Patient-derived xenografts (PDXs) have emerged as an informative, renewable experimental resource to model CRC architecture and biology. Here, we describe the generation of a biobank of CRC PDXs from stage I to stage IV patients. We demonstrate that PDXs within our biobank recapitulate the histopathological and mutation features of the original patient tumor. In addition, we demonstrate the utility of this resource in pre-clinical chemotherapy and targeted treatment studies, highlighting the translational potential of PDX models in the identification of new therapies that will improve the overall survival of CRC patients.
ABSTRACT
Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly to the regulation of homeostasis. We have shown that from early embryonic development Bcl-G, a Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal epithelial cells. While Bcl-G was dispensable for normal growth and development in mice, the loss of Bcl-G resulted in accelerated progression of colitis-associated cancer. A label-free quantitative proteomics approach revealed that Bcl-G may contribute to the stability of a mucin network, which when disrupted, is linked to colon tumorigenesis. Consistent with this, we observed a significant reduction in Bcl-G expression in human colorectal tumors. Our study identifies an unappreciated role for Bcl-G in colon cancer.
Subject(s)
Colorectal Neoplasms/metabolism , Inflammation/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Animals , Colitis/metabolism , Colitis/pathology , Colorectal Neoplasms/pathology , Humans , Inflammation/pathology , Mice , Mice, Knockout , Proto-Oncogene Proteins c-bcl-2/deficiency , Proto-Oncogene Proteins c-bcl-2/geneticsABSTRACT
Interleukin (IL)-11 belongs to the IL-6 family of cytokines, discovered over 30 years ago. While early studies focused on the ability of IL-11 to stimulate megakaryocytopoiesis, the importance of this cytokine to inflammatory disease and cancers is only just beginning to be uncovered. This review outlines recent advances in our understanding of IL-11 biology, and highlights the development of novel therapeutics with the potential for clinical targeting of signaling by this cytokine in multiple diseases.
