Dermal fibroblasts promote cancer cell proliferation and exhibit fibronectin overexpression in early mycosis fungoides.
Dermal fibroblasts promote cancer cell proliferation and exhibit fibronectin overexpression in early mycosis fungoides.
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DOI：
10.1016/j.jdermsci.2022.03.005
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发表时间：
2022-04
影响因子：
4.6
通讯作者：
Nikbakht, Neda
中科院分区：
文献类型：
--
作者：
Beksac, Burcu;Gleason, Laura;Baik, Sarah;Ringe, John M.;Porcu, Pierluigi;Nikbakht, Neda
蕈样肉芽肿（MF）是由皮肤中恶性T细胞增殖引起的，并可能进展到累及血液、淋巴结和内脏。虽然皮肤微环境对于MF的早期阶段的起始和进展是必不可少的，但是关于皮肤基质对恶性淋巴细胞的生长和存活的影响知之甚少。我们研究了真皮成纤维细胞及其产物纤维连接蛋白对恶性MF细胞存活和增殖的影响。从早期MF患者的皮肤中分离成纤维细胞和恶性MF CD 4 T细胞。利用来源于病变皮肤、血液和MF细胞系的细胞建立成纤维细胞-淋巴细胞共培养实验和纤连蛋白包被的平板上的淋巴细胞培养。用Annexin V法和羧基荧光素琥珀酰亚胺酯法检测淋巴细胞的存活率和增殖率。此外，通过免疫荧光法评估MF皮肤中的整合素和纤连蛋白表达。我们发现，真皮成纤维细胞增加MF细胞的增殖率，但不是正常皮肤或血液CD 4 T细胞。然而，成纤维细胞并没有拯救MF细胞凋亡的共培养。在MF皮肤中，我们发现了正常情况下在健康皮肤中不存在的纤连蛋白亚型的过度表达。MF细胞表达纤连蛋白结合整合素并粘附于纤连蛋白，但未表现出通过纤连蛋白-整合素相互作用的粘附介导的存活。总体而言，我们的研究结果表明，成纤维细胞，独立的纤连蛋白介导的粘附，在促进MF细胞增殖的直接作用。这些发现对理解和靶向皮肤淋巴瘤中的恶性皮肤基质微环境具有意义。
Mycosis fungoides (MF) is caused by proliferation of malignant T-cells in the skin and may progress to involve blood, lymph nodes, and viscera. While the skin microenvironment is essential for the initiation and progression of MF in early stages, little is known about the impact of skin stroma on the growth and survival of malignant lymphocytes. We investigated the effect of dermal fibroblasts and their product, fibronectin, on the survival and proliferation of malignant MF cells. Fibroblasts and malignant MF CD4 T-cells were isolated from skin of patients with early-stage MF. Fibroblast-lymphocyte co-culture experiments and lymphocyte cultures on fibronectin-coated plates were established utilizing the cells derived from lesional skin, blood, and MF cell lines. The survival and proliferation rates of lymphocytes were assessed via Annexin V and carboxyfluorescein succinimidyl ester assays respectively. Additionally, integrin and fibronectin expressions in MF skin were assessed via immunofluorescence. We found that dermal fibroblasts increased the proliferation rates of MF cells, but not normal skin or blood CD4 T-cells. However, fibroblasts did not rescue MF cells from apoptosis in co-cultures. In MF skin, we found an overexpression of a fibronectin isoform not normally found in healthy skin. MF cells expressed fibronectin-binding integrins and adhered to fibronectin but did not exhibit adhesion-mediated survival via fibronectin-integrin interactions. Overall, our results suggest a direct role for fibroblasts, independent of fibronectin-mediated adhesion, in promoting MF cell proliferation. These findings have implications in understanding and targeting the malignant skin stromal microenvironment in cutaneous lymphomas.
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影响因子：
5.6
作者：
SMOLLER, BR;BISHOP, K;HENDRICKSON, M
通讯作者：
HENDRICKSON, M
皮肤T细胞淋巴瘤中的新疗法和免疫学发现。
影响因子：
4.7
作者：
Fujii K
通讯作者：
Fujii K
影响因子：
3.9
作者：
Wang JP;Hielscher A
通讯作者：
Hielscher A
影响因子：
6.5
作者：
Aronovich, Anna;Moyal, Lilach;Hodak, Emmilia
通讯作者：
Hodak, Emmilia
影响因子：
5.3
作者：
Liu, Chi-Chao;Leclair, Pascal;Lim, Chinten James
通讯作者：
Lim, Chinten James