TGFß increases production of ANGPTL4, which allows cancerous cells to enter the lungs, according to Cell paper.

Researchers found evidence that the cytokine TGFß in the tumor microenvironment primes breast cancer cells for metastasis to the lungs, one of the most common sites for the spread of breast and other cancers. TGFß signaling is often activated within tumors as a natural response to the oxygen starved and inflammatory conditions that come with tumor progression.


The scientists analyzed the expression of all 20,000 genes in the human genome within hundreds of primary breast tumors. Those tumors fell within two classical groups based on whether their estrogen receptor status was positive or negative (ER+ or ER-). In both tumor groups, the researchers found that about 40% of the tumors bore the genetic signature of TGFß’s influence.


They found that TGFß exposure didn’t seem to make any difference to the risk of cancer spread in ER+ tumors. In ER- tumors, however, TGFß correlated markedly with an increased risk for metastasis to the lung, but not to bone.


Furthermore the investigators discovered 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, the scientists reported.


The investigators involved came from the Memorial Sloan-Kettering Cancer Center, Hospital Clinic-IDIBAPS, and the Institute for Research in Biomedicine. The study will be published in the April 4 issue of Cell.

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