Blocking Periostin Prevents Metastasis in a Mouse Cancer Model

Cancer researchers have identified a protein that seems to be required for cancer cells to metastasize successfully and established secondary tumors at sites distantly removed from the original primary tumor.

Metastatic growth in distant organs is the major cause of cancer mortality, yet this process is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites.

Investigators at the Swiss Center for Experimental Cancer Research (Lausanne, Switzerland) worked with a mouse model to look for molecular keys that could enhance a tumor's ability to establish secondary tumors successfully.

They reported in the December 7, 2011, online edition of the journal Nature that a small population of cancer stem cells was critical for metastatic colonization, and that stromal niche signals expressed by potential sites of colonization were crucial to the expansion process. They found that the protein periostin (POSTN), a component of the extracellular matrix, was expressed by fibroblasts in normal tissue and in the stroma of the primary tumor. Infiltrating tumor cells needed to induce stromal POSTN expression in the secondary target organ to initiate colonization. POSTN was required to allow cancer stem cell maintenance, and blocking its function prevented metastasis.

The investigators showed that several conditions were necessary for cancer to propagate. "In particular, we were able to isolate a protein, periostin, in the niches where metastases develop," said senior author Dr. Joerg Huelsken, professor of molecular oncology at the Swiss Center for Experimental Cancer. "Without this protein, the cancer stem cell cannot initiate metastasis; instead, it disappears or remains dormant."

Experimental treatments that blocked periostin activity produced very few side effects in mice, but the investigators caution that this does not necessarily mean the same will hold true in humans.

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Swiss Center for Experimental Cancer Research