Cure Alveolar Soft Part Sarcoma International (iCureASPS)

New article about research study initiated by our Yosef Landesman, Ph.D. President & Cancer Research Director Cure Alveolar Soft Part Sarcoma International (iCureASPS) Myofibroblasts in pulmonary and brain metastases of alveolar soft-part sarcoma: a novel target for treatment?
http://www.ncbi.nlm.nih.gov/pubmed/18714394
is now indexed for the Pubmed which makes it readily available for access by anyone interested.

Thank you Yossi and all for your concerted efforts to bring knowledge of ASPS, and what it brings to the table, to the masses . As well as the international community .
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The Pearson’s


Abstract

Alveolar soft-part sarcoma (ASPS) is a rare neoplasm with chromosomal translocation that results in ASPL-TFE3 fusion. It is a slow-growing lesion associated with a high incidence of pulmonary and brain metastases indicating poor survival. We demonstrated that the ASPS metastases include also stromal myofibroblasts. These cells proliferate, express smooth-muscle genes, and synthesize extracellular matrix proteins, all of which are characteristics of activated myofibroblasts. The tumor cells also exhibited stromal components such as transforming growth factor beta (TGFβ)-dependent, hypoxia-regulated cytoglobin (stellate cell activation association protein, cytg/STAP) and prolyl 4-hydroxylase, a collagen cross-linking enzyme. The pulmonary ASPS myofibroblasts synthesize serum response factor (SRF), a repressor of Smad3-mediated TGFβ signaling essential for myofibroblast differentiation and Smad3. The phosphorylated active Smad3 was found mostly in the tumor cells. The brain tumor cells express cytg/STAP, but in contrast to the lung metastases, they also express SRF, Smad3, and phospho-Smad3. Halofuginone, an inhibitor of myofibroblasts' activation and Smad3 phosphorylation, inhibited tumor development in xenografts derived from renal carcinoma cells harboring a reciprocal ASPL-TFE3 fusion transcript. This inhibition was associated with the inhibition of TGFβ/SRF signaling, with the inhibition of myofibroblasts' activation, and with the complete loss in TFE3 synthesis by the tumor cells. These results suggest that the myofibroblasts may serve as a novel target for treatment of ASPS metastases.