Human breast tumors' 'microenvironment' primes them for metastasis

The researchers continued to dig, ultimately uncovering the “fascinating biology” behind that correlation. They found that the TGFß exposure in ER- tumors leads to an increase in a second cytokine within the tumor cells, called angiopoietin-like 4 (ANGPTL4). Once those cells escape the tumor and lodge in the lungs, ANGPTL4 disrupts the connections between cells in the thin capillaries there. That separation of cell-cell contacts allows the cancer cells to cross the vessel wall and pass into the lung proper, Massague said.

The findings suggest that TGFß, or perhaps even better ANGPTL4, might serve as targets for drugs aimed at preventing the spread of breast cancer to the lungs. The TGFß signature could also offer a means of predicting those breast cancer patients at particularly high risk for developing metastatic lung cancer so that they might be monitored more closely and treated more aggressively with existing drugs.

Massague said he suspects the new findings are but one example of a more general cancer phenomenon.

“Entering and colonizing an organ requires of a tumor cell a number of special abilities,” he said. After all, “our bodies are not made up of cells that are allowed to go anywhere as tumor cells [sometimes] manage to do. We’ve shown that factors within primary tumors can act on cancer cells to enhance their ability” to selectively spread to other tissues.

Researchers include David Padua, Memorial Sloan-Kettering Cancer Center, New York, New York; Xiang H-F. Zhang, Memorial Sloan-Kettering Cancer Center, New York, New York; Qiongqing Wang, Memorial Sloan-Kettering Cancer Center, New York, New York; Cristina Nadal, Institut de Malalties Hemato-Oncologiques, Hospital Clinic-IDIBAPS, Barcelona, Spain; William L. Gerald, Memorial Sloan-Kettering Cancer Center, New York, New York; Roger R. Gomis, Oncology Programme, Institute for Research in Biomedicine, Barcelona, Spain; and Joan Massague, Memorial Sloan-Kettering Cancer Center, New York, New York, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York.