Irina Alho1, Luis Costa2, Manuel Bicho3, Constança Coelho4. 1. Genetics Laboratory, Environmental Health Institute (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. 2. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal Serviço de Oncologia Médica, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte, Lisbon, Portugal. 3. Genetics Laboratory, Environmental Health Institute (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal Instituto Rocha Cabral Lisboa, Lisbon, Portugal. 4. Genetics Laboratory, Environmental Health Institute (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal constancacoelho@medicina.ulisboa.pt.
Abstract
BACKGROUND/AIM: During the bone metastatic process, tumor cells and bone cells drive a vicious cycle stimulating growth and activity of each other. We here address how low molecular weight protein tyrosine phosphatase (LMW-PTP) could be involved in this process. MATERIALS AND METHODS: We targeted LMW-PTP by siRNA and evaluated the effect of various soluble factors released to the culture medium by the MDA-MB-435 breast cancer cell line, in RAW 264.7 osteoclastogenesis. RESULTS: We showed that these soluble factors did not change RAW 264.7 osteoclastogenic potential. The knockdown of the LMW-PTP slow isoform decreased osteoclastogenesis of RAW 264.7, showing less active Src. The knockdown of LMW-PTP and its slow isoform decreased the release of IL-8 but not IL-6 in MDA-MB-435. CONCLUSION: The LMW-PTP slow isoform can be an important protein in bone metastatic disease, with a fundamental role in the interplay between tumor cells and osteoclasts, through the regulation of Src activity and IL-8 secretion. Copyright
BACKGROUND/AIM: During the bone metastatic process, tumor cells and bone cells drive a vicious cycle stimulating growth and activity of each other. We here address how low molecular weight protein tyrosine phosphatase (LMW-PTP) could be involved in this process. MATERIALS AND METHODS: We targeted LMW-PTP by siRNA and evaluated the effect of various soluble factors released to the culture medium by the MDA-MB-435 breast cancer cell line, in RAW 264.7 osteoclastogenesis. RESULTS: We showed that these soluble factors did not change RAW 264.7 osteoclastogenic potential. The knockdown of the LMW-PTP slow isoform decreased osteoclastogenesis of RAW 264.7, showing less active Src. The knockdown of LMW-PTP and its slow isoform decreased the release of IL-8 but not IL-6 in MDA-MB-435. CONCLUSION: The LMW-PTP slow isoform can be an important protein in bone metastatic disease, with a fundamental role in the interplay between tumor cells and osteoclasts, through the regulation of Src activity and IL-8 secretion. Copyright