Cancer Metastasis: Building a Framework

Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion

TGFβ in Cancer

Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.

Mesenchymal stem cells within tumour stroma promote breast cancer metastasis

It is widely accepted that the development of carcinoma--the most common form of human cancer--is due to the accumulation of somatic mutations in epithelial cells. The behaviour of carcinomas is also influenced by the tumour microenvironment, which includes extracellular matrix, blood vasculature, inflammatory cells and fibroblasts. Recent studies reveal that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated. These new findings have important therapeutic implications.

Stromal fibroblasts in cancer initiation and progression

Molecular characterization of the tumor microenvironment in breast cancer

The invention features nucleic acids encoding proteins that are expressed at a higher or a lower level in breast cancer cells than in normal breast cells or in a cell of one grade or stage of breast cancer than in a cell of another grade or stage of breast cancer. The invention also includes proteins encoded by the nucleic acids, vectors containing the nucleic acids, and cells containing the vectors. In another aspect, the invention features methods of diagnosing and treating breast cancers of various grades and stages.

Minna Allinen

Papers

Molecular characterization of the tumor microenvironment in breast cancer

Gene expression in breast cancer