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Researchers Unravel Clues to Lung Cancer Metastasis

Connective tissue growth factor may inhibit VEGF-regulating transcription factor

WEDNESDAY, July 19 (HealthDay News) -- Connective tissue growth factor, or CTGF, which is known to inhibit human lung cancer metastasis in a mouse model, apparently does so by blocking vascular endothelial growth factor-A (VEGF-A)-related angiogenesis, according to a study in the July 19 issue of the Journal of the National Cancer Institute. CTGF appears to inhibit hypoxia-inducible factor-1alpha (HIF-1α), a transcription factor that controls VEGF expression, so that blocking HIF-1α may be an effective cancer therapy.

Min-Liang Kuo, Ph.D., of National Taiwan University in Taipei, Taiwan, and colleagues transfected human lung adenocarcinoma cells with vectors containing CTGF, HIF-1α and/or controls. They then injected the transfected cells into 10 nude mice per group and measured tumor growth, metastasis and mouse survival.

The researchers found that xenograft tumors derived from CTGF transfectants grew more slowly than those from controls and had reduced expression of HIF-1α, VEGF-A, vascularization and metastasis. When CTGF was silenced, xenografts grew faster and vascularization was increased, the report indicates.

CTGF alone or with other molecules such as antisense arrest-defective-1 protein can inhibit angiogenesis, and HIF-1α may be an important mediator of the process, the authors conclude.

Whether the new findings are restricted to lung cancer is not yet known, but they do "provide mechanistic insight of how CTGF exerts a potent growth-inhibiting and anti-metastatic effect," write editorialists in an accompanying commentary.

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