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June 25, 2007

Scientists Show Protein Accelerates Breast Cancer Progression in Animal Models

Topics: Medicine

angiogenesis6.jpgNew findings demonstrate the significance of pleiotrophin (PTN) expression in breast cancer, which could not only lead to a better understanding of the molecular pathogenesis of breast cancer but also focus attention on PTN and its signaling pathway as possible targets for new cancer therapies.

The study also found that the expression of pleiotrophin activated surrounding cells to remodel the tumor microenvironment, induced tumor angiogenesis, and increased the number of receptors for different markers of aggressive breast cancers.

"Breast cancers progress through stages of increasing malignancy triggered by mutations that promote their growth," said Thomas Deuel, the Scripps Research scientist whose laboratory made the discovery. "The major finding of our study demonstrates both in vivo and in vitro that inappropriate expression of PTN not only promotes breast cancer progression but that by itself PTN secretion from human breast cancer cells may be sufficient to shift that progression to a more aggressive form of breast cancer."

In the study, three models were tested to determine if inappropriate expression of PTN alone was sufficient to induce breast cancer or whether the cytokine cooperates with different pathogenic mechanisms to stimulate breast cancer progression.

The new study identified PTN as one factor that activates stromal cells-cells found in the loose connective tissue-and induces several features of aggressive breast cancer. While the importance of these cancer cell-stromal cell interactions is well established, only limited progress has been made in identifying the factors that cause stromal cells to initiate tumor progression.

"Our breakthrough findings demonstrate that PTN-activated stromal cells are responsible for the ultimate remodeling of extracellular matrix proteins, as well as the release of factors that stimulate the growth of malignant cancer cells," Deuel said. "We've shown that PTN secreted from breast cancer cells is the key mechanism of stromal cell activation, and that PTN alone is sufficient to stimulate many of the critical signaling pathways that aggressively promote breast cancer progression."

More at News-Medical.Net ...

Angiogenesis, the recruitment of new blood vessels, is an essential component of the metastatic pathway. These vessels provide the principal route by which tumor cells exit the primary tumor site and enter the circulation. For many tumors, the vascular density can provide a prognostic indicator of metastatic potential, with the highly vascular primary tumors having a higher incidence of metastasis than poorly vascular tumors. Tumor angiogenesis is regulated by the production of angiogenic stimulators including members of the fibroblast growth factor and vascular endothelial growth factor families. In addition, tumors may activate angiogenic inhibitors such as angiostatin and endostatin that can modulate angiogenesis both at the primary site and at downstream sites of metastasis. The potential use of these and other natural and synthetic angiogenic inhibitors as anticancer drugs is currently under intense investigation. Such agents may have reduced toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Clinical trials are now underway to develop optimum treatment strategies for antiangiogenic agents.

Related:
Secretion of pleiotrophin stimulates breast cancer progression through remodeling of the tumor microenvironment

Cross posted from New Hope Blog

Posted by Richard at June 25, 2007 12:10 AM



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