Objective:Osteosarcoma(OS)is an aggressive,highly metastatic,relatively drug-resistant bone tumor with poor long-term survival rates.The presence and persistence of circulating tumor cells(CTCs)in the peripheral blood...Objective:Osteosarcoma(OS)is an aggressive,highly metastatic,relatively drug-resistant bone tumor with poor long-term survival rates.The presence and persistence of circulating tumor cells(CTCs)in the peripheral blood are believed to be associated with treatment inefficiency and distant metastases.A blood-based CTC test is thus greatly needed for monitoring disease progression and predicting clinical outcomes.However,traditional methods cannot detect CTCs from tumors of mesenchymal origin such as OS,and research on CTC detection in mesenchymal tumors has been hindered for years.Methods:In this study,we developed a CTC test based on hexokinase 2,a metabolic function-associated marker,for the detection and surveillance of OS CTCs,and subsequently explored its clinical value.Twelve patients with OS were enrolled as the training cohort for serial CTC tests.Dynamic CTC counting,in combination with therapy evaluation and post-treatment follow-up,was used to establish a model for predicting post-chemotherapy evaluation and disease-free survival,and the model was further validated with a cohort of 8 patients with OS.Results:Two dynamic CTC number patterns were identified,and the resulting predictive model exhibited 92%consistency with the clinical outcomes.This model suggested that a single CTC test has similar predictive power to serial CTC analysis.In the validation cohort,the single CTC test exhibited 100%and 87.5%consistency with therapy response and disease-free survival,respectively.Conclusions:Our non-invasive test for detection and surveillance of CTCs enables accurate prediction of therapy efficiency and prognosis,and may be clinically valuable for avoiding inefficient therapy and prolonging survival.展开更多
Objective: To examine the role of store-operated calcium entry(SOCE) and stromal interaction molecule 1(STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca^(2+)con...Objective: To examine the role of store-operated calcium entry(SOCE) and stromal interaction molecule 1(STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca^(2+)contributes to the regulation of osteosarcoma cells.Methods: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1(NFATc1)activity by luciferase assays.Results: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca^(2+) channels involved down-regulation of NFATc1 in osteosarcoma cells.Conclusions: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca^(2+) entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.21775103 to Q.S.,Grant No.82172366 to L.Y.,and Grant No.81802985 to D.Z.)Shanghai Science and Technology Committee(Grant No.20ZR1473000 to Q.S.).
文摘Objective:Osteosarcoma(OS)is an aggressive,highly metastatic,relatively drug-resistant bone tumor with poor long-term survival rates.The presence and persistence of circulating tumor cells(CTCs)in the peripheral blood are believed to be associated with treatment inefficiency and distant metastases.A blood-based CTC test is thus greatly needed for monitoring disease progression and predicting clinical outcomes.However,traditional methods cannot detect CTCs from tumors of mesenchymal origin such as OS,and research on CTC detection in mesenchymal tumors has been hindered for years.Methods:In this study,we developed a CTC test based on hexokinase 2,a metabolic function-associated marker,for the detection and surveillance of OS CTCs,and subsequently explored its clinical value.Twelve patients with OS were enrolled as the training cohort for serial CTC tests.Dynamic CTC counting,in combination with therapy evaluation and post-treatment follow-up,was used to establish a model for predicting post-chemotherapy evaluation and disease-free survival,and the model was further validated with a cohort of 8 patients with OS.Results:Two dynamic CTC number patterns were identified,and the resulting predictive model exhibited 92%consistency with the clinical outcomes.This model suggested that a single CTC test has similar predictive power to serial CTC analysis.In the validation cohort,the single CTC test exhibited 100%and 87.5%consistency with therapy response and disease-free survival,respectively.Conclusions:Our non-invasive test for detection and surveillance of CTCs enables accurate prediction of therapy efficiency and prognosis,and may be clinically valuable for avoiding inefficient therapy and prolonging survival.
基金supported by Mayo Clinic, USA and Peking University People’s Hospital, Beijing, China
文摘Objective: To examine the role of store-operated calcium entry(SOCE) and stromal interaction molecule 1(STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca^(2+)contributes to the regulation of osteosarcoma cells.Methods: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1(NFATc1)activity by luciferase assays.Results: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca^(2+) channels involved down-regulation of NFATc1 in osteosarcoma cells.Conclusions: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca^(2+) entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.