Yuanyuan Li1,2, Ling Gu3,4. 1. Laboratory of Hematology/Oncology, Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, 610041, People's Republic of China. 2. Joint Laboratory of West China Second University Hospital, Sichuan University and School of Life Science, Fudan University for Pulmonary Development and Disease, Chengdu, 610041, China. 3. Laboratory of Hematology/Oncology, Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, 610041, People's Republic of China. guling@scu.edu.cn. 4. Joint Laboratory of West China Second University Hospital, Sichuan University and School of Life Science, Fudan University for Pulmonary Development and Disease, Chengdu, 610041, China. guling@scu.edu.cn.
Abstract
BACKGROUND: Chemo-resistance is still a major obstacle in leukemia treatment. Accumulating evidence indicates that cancer-associated fibroblasts (CAFs), the most abundant stromal cells in tumor microenvironment (TME), play a crucial role in cancer progression and response to chemotherapy. To Figure out the role of leukemia-associated fibroblasts (LAFs) in relapsed/refractory leukemia, we constructed the first leukemia-associated fibroblastic tumor cell line, HXWMF-1. METHODS: A cell culture technique was used to establish the leukemia-associated fibroblastic tumor cell line. Molecular and cellular biological techniques including flow cytometry, MTT assay, western blotting, and short tandem repeat (STR) analysis were used to characterize the cell line. Nude mice were used for xenograft studies. RESULTS: We established a LAFs derived tumor cell line HXWMF-1, originated from the subcutaneous xenografts of HXEX-ALL1, a cell line originated from a patient with acute lymphoblastic leukemia (ALL) at the second relapse. The HXWMF-1 cell line was authenticated as a tumor cell line and being derived from CAFs based on morphologic, immunophenotypic, cytogenetic and STR analyses and tumorigenicity test in nude mice. To clarify the reliability of the method, we got the LAFs derived tumor cells from three different tumor mass of HXEX-ALL1 xenografts. CONCLUSIONS: To our knowledge, HXWMF-1 is the first fibroblastic tumor cell line derived from LAFs or CAFs. In addition, the cell line provided firm evidence for that leukemia cells may induce LAFs/CAFs malignant transformation, which may help to develop brand new theory and therapeutic strategies for patients with relapsed /refractory ALL.
BACKGROUND: Chemo-resistance is still a major obstacle in leukemia treatment. Accumulating evidence indicates that cancer-associated fibroblasts (CAFs), the most abundant stromal cells in tumor microenvironment (TME), play a crucial role in cancer progression and response to chemotherapy. To Figure out the role of leukemia-associated fibroblasts (LAFs) in relapsed/refractory leukemia, we constructed the first leukemia-associated fibroblastic tumor cell line, HXWMF-1. METHODS: A cell culture technique was used to establish the leukemia-associated fibroblastic tumor cell line. Molecular and cellular biological techniques including flow cytometry, MTT assay, western blotting, and short tandem repeat (STR) analysis were used to characterize the cell line. Nude mice were used for xenograft studies. RESULTS: We established a LAFs derived tumor cell line HXWMF-1, originated from the subcutaneous xenografts of HXEX-ALL1, a cell line originated from a patient with acute lymphoblastic leukemia (ALL) at the second relapse. The HXWMF-1 cell line was authenticated as a tumor cell line and being derived from CAFs based on morphologic, immunophenotypic, cytogenetic and STR analyses and tumorigenicity test in nude mice. To clarify the reliability of the method, we got the LAFs derived tumor cells from three different tumor mass of HXEX-ALL1 xenografts. CONCLUSIONS: To our knowledge, HXWMF-1 is the first fibroblastic tumor cell line derived from LAFs or CAFs. In addition, the cell line provided firm evidence for that leukemia cells may induce LAFs/CAFs malignant transformation, which may help to develop brand new theory and therapeutic strategies for patients with relapsed /refractory ALL.
Authors: Allison R Pine; Stefano M Cirigliano; James G Nicholson; Yang Hu; Amanda Linkous; Ken Miyaguchi; Lincoln Edwards; Richa Singhania; Theodore H Schwartz; Rohan Ramakrishna; David J Pisapia; Matija Snuderl; Olivier Elemento; Howard A Fine Journal: Cancer Discov Date: 2020-04-06 Impact factor: 39.397
Authors: Mikhail Binnewies; Edward W Roberts; Kelly Kersten; Vincent Chan; Douglas F Fearon; Miriam Merad; Lisa M Coussens; Dmitry I Gabrilovich; Suzanne Ostrand-Rosenberg; Catherine C Hedrick; Robert H Vonderheide; Mikael J Pittet; Rakesh K Jain; Weiping Zou; T Kevin Howcroft; Elisa C Woodhouse; Robert A Weinberg; Matthew F Krummel Journal: Nat Med Date: 2018-04-23 Impact factor: 53.440