Malignant cells facilitate lung metastasis by bringing their own soil

DG Duda, AMMJ Duyverman… - Proceedings of the …, 2010 - National Acad Sciences
DG Duda, AMMJ Duyverman, M Kohno, M Snuderl, EJA Steller, D Fukumura, RK Jain
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
Metastatic cancer cells (seeds) preferentially grow in the secondary sites with a permissive
microenvironment (soil). We show that the metastatic cells can bring their own soil—stromal
components including activated fibroblasts—from the primary site to the lungs. By analyzing
the efferent blood from tumors, we found that viability of circulating metastatic cancer cells is
higher if they are incorporated in heterotypic tumor–stroma cell fragments. Moreover, we
show that these cotraveling stromal cells provide an early growth advantage to the …
Metastatic cancer cells (seeds) preferentially grow in the secondary sites with a permissive microenvironment (soil). We show that the metastatic cells can bring their own soil—stromal components including activated fibroblasts—from the primary site to the lungs. By analyzing the efferent blood from tumors, we found that viability of circulating metastatic cancer cells is higher if they are incorporated in heterotypic tumor–stroma cell fragments. Moreover, we show that these cotraveling stromal cells provide an early growth advantage to the accompanying metastatic cancer cells in the lungs. Consistent with this hypothesis, we demonstrate that partial depletion of the carcinoma-associated fibroblasts, which spontaneously spread to the lung tissue along with metastatic cancer cells, significantly decreases the number of metastases and extends survival after primary tumor resection. Finally, we show that the brain metastases from lung carcinoma and other carcinomas in patients contain carcinoma-associated fibroblasts, in contrast to primary brain tumors or normal brain tissue. Demonstration of the direct involvement of primary tumor stroma in metastasis has important conceptual and clinical implications for the colonization step in tumor progression.
National Acad Sciences