A poster presented last month at the 2009 American Association for Cancer Research (AACR) Annual Meeting in Denver, CO, announced a breakthrough in research that aims to find a cure for ASPS.
For the first time, a team of researchers, among them Dr. David Vistica, reported their success in the establishment of a stable Alveolar Soft Part Sarcoma cell line for the first time. The origin of this cell line is from a lymph node metastasis which was donated by a female patient. Very importantly, the cell line was carefully tested and was found to maintain the characteristics of the original ASPS tumor for over three years.
This cell line will facilitate investigations into the biology of ASPS, and aid in the pre-clinical identification of new ASPS therapeutics. Here below is the abstract of the poster:
Establishment and characterization of ASPS-1, a novel cell line derived from metastatic alveolar soft part sarcoma
Investigation into the biology of Alveolar Soft Part Sarcoma (ASPS) and preclinical evaluation of potential ASPS therapeutics have been severely hampered by the lack of both in vitro and in vivo models of this soft tissue sarcoma. Recently we have described an in vivo xenograft model of ASPS in sex-matched NOD.SCID\NCr mice. This model, established from a lymph node metastasis from a female patient, has maintained characteristics consistent with those of the original ASPS tumor for over 3 years. Characteristics studied include: (1) tumor histology and staining with Periodic Acid Schiff/Diastase, (2) the presence of the ASPL-TFE3 type 1 fusion transcript, (3) nuclear staining with antibodies to the ASPL-TFE3 type 1 fusion protein, (4) maintenance of the t(X;17)(p11;q25) translocation characteristic of ASPS, (5) stable expression of signature ASPS gene transcripts and finally, the development and maintenance of a functional vascular network, a hallmark of ASPS. Utilizing this ASPS xenografted tumor we have successfully developed the first cell line of this rare pediatric sarcoma. Organoid nests consisting of 15-25 ASPS cells were isolated from ASPS xenograft tumors by capture on 70 um filters and plated in vitro. Following attachment to the substratum, these nests deposited small aggregates of ASPS cells. Over a period of 1.5 years, these cells were expanded and monitored for the following: ASPL-TFE3 type 1 fusion transcript, the t(X;17)(p11;q25) translocation and expression of up regulated ASPS transcripts involved in angiogenesis (ANGPTL2, HIF1 alpha, MDK, MET,VEGF, TIMP-2) , cell proliferation (PRL, PCSK1, IGFBP1), metastasis (ADAM9) as well as the transcription factor BHLHB3 and the muscle specific transcripts TRIM63 and ITGB1BP3. This ASPS cell line forms colonies in soft agar and retains the ability to produce highly vascularized ASPS tumors in NOD.SCID\NCr mice. Immunohistochemistry of selected ASPS markers on these tumors indicated similarity to those of the original patient tumor as well as to xenografted ASPS tumors. This ASPS cell line will facilitate investigation into the biology of ASPS and aid in the pre-clinical identification of new ASPS therapeutics.
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Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com