Li Yuanyuan, Gu Ling
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.
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.
Cancer Cell Int. 2021 Mar 19;21(1):177. doi: 10.1186/s12935-021-01870-7.
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.
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.
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.
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.
化疗耐药仍然是白血病治疗中的主要障碍。越来越多的证据表明，癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）中最丰富的基质细胞，在癌症进展和化疗反应中起关键作用。为了弄清楚白血病相关成纤维细胞（LAFs）在复发/难治性白血病中的作用，我们构建了首个白血病相关成纤维细胞瘤细胞系HXWMF-1。
采用细胞培养技术建立白血病相关成纤维细胞瘤细胞系。使用包括流式细胞术、MTT 法、蛋白质印迹法和短串联重复序列（STR）分析在内的分子和细胞生物学技术对该细胞系进行表征。使用裸鼠进行异种移植研究。
我们建立了一个源自LAFs的肿瘤细胞系HXWMF-1，它起源于HXEX-ALL1的皮下异种移植瘤，HXEX-ALL1是一个源自一名急性淋巴细胞白血病（ALL）患者第二次复发时的细胞系。基于形态学、免疫表型、细胞遗传学和STR分析以及在裸鼠中的致瘤性测试，HXWMF-1细胞系被鉴定为肿瘤细胞系且源自CAFs。为了阐明该方法的可靠性，我们从HXEX-ALL1异种移植瘤的三个不同肿瘤块中获得了源自LAFs的肿瘤细胞。
据我们所知，HXWMF-1是首个源自LAFs或CAFs的成纤维细胞瘤细胞系。此外，该细胞系为白血病细胞可能诱导LAFs/CAFs恶性转化提供了确凿证据，这可能有助于为复发/难治性ALL患者开发全新的理论和治疗策略。
