Abstract C8: Bone metastasis seed preselection by the primary tumor stroma

Abstract

Abstract A key question in understanding the origin of metastasis is how cancer cells in a primary tumor acquire the ability to colonize a distant organ. Here we provide one answer to this puzzle by proposing the “metastasis seed pre-selection” model: when the stroma of a primary tumor resembles that of a distant organ, it pre-selects cancer cells that are predisposed to survive in that organ. In breast cancer, the mesenchymal stromal components cancer-associated fibroblasts (CAFs) create a microenvironment similar to that of the bone marrow. Heterogeneous cancer cell populations growing in a CAF-rich breast tumor are skewed towards a preponderance of clones with a superior ability to survive and proliferate on the environmental cues CAFs produce. When these cancer cell clones metastasize and infiltrate the bone marrow, they can maximally exploit these cues familiar to them for initial survival. As a result, these cells have a better chance to colonize the bone when they metastasize. Thus, a CAF-rich stroma primes the breast tumor as a whole at risk of developing bone metastasis. Our findings have implications for the evolution of metastatic traits and the interplay between a primary tumor and its distant metastases. Citation Format: Xiang Zhang, Xin Jin, Srinivas Malladi, Yong Wen, Edi Brogi, Joan Massague. Bone metastasis seed preselection by the primary tumor stroma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C8.