Ohana Ofra Malka, Ozer Janet, Prinsloo Isebrand, Benharroch Daniel, Gopas Jacob
a Department of Microbiology ; Immunology and Genetics; Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.
b Department of Pathology ; Soroka University Medical Center; and Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.
Cancer Biol Ther. 2015;16(11):1651-9. doi: 10.1080/15384047.2015.1095411. Epub 2015 Sep 29.
Hodgkin's lymphoma is believed to spread in an orderly fashion within the lymphatic compartment. In a minority of cases, after reaching the spleen, the neoplasm disseminates, reminiscent of metastasis. In the spleen, the Hodgkin-Reed-Sternberg tumor cells come across platelets in the blood vessels and mainly in the splenic red pulp. Based on this knowledge, we investigated the possibility of platelets inducing cell adhesion in Hodgkin's lymphoma cell lines. We showed that L428 and KMH-2 cells strongly adhere to thrombin-activated platelets. Cell adhesion to platelets is partially dependent on CD15 antigens (Lewis(X)), mainly sialyl-CD15, and P-selectin. KMH-2, as compared to L428 cells, showed increased binding due to its differential high expression of the sialyl-CD15. As a consequence of incubation with platelets, KMH-2 cells also produced increased amounts of tumor necrosis factors α (TNFα) followed by enhanced binding to human vascular endothelial cells (HUVEC). Incubation of both cell lines with activated platelets also induced activation of AP-1 transcription complex. Our findings are consistent with the concept that platelets play a critical role in the dissemination of HRS cells in HL, predominantly in the spleen, by increasing cell adhesion and thus promoting their proliferative and migratory properties beyond the lymphatic system.
霍奇金淋巴瘤被认为在淋巴系统内按顺序扩散。在少数情况下,肿瘤到达脾脏后会播散,类似转移。在脾脏中,霍奇金-里德-斯特恩伯格肿瘤细胞在血管中,主要是在脾红髓中遇到血小板。基于这一认识,我们研究了血小板诱导霍奇金淋巴瘤细胞系细胞黏附的可能性。我们发现L428和KMH-2细胞能强烈黏附于凝血酶激活的血小板。细胞与血小板的黏附部分依赖于CD15抗原(Lewis(X)),主要是唾液酸化CD15和P-选择素。与L428细胞相比,KMH-2细胞由于其唾液酸化CD15的差异高表达而表现出更强的结合能力。与血小板孵育后,KMH-2细胞还产生了更多的肿瘤坏死因子α(TNFα),随后与人类血管内皮细胞(HUVEC)的结合增强。用活化血小板孵育这两种细胞系也诱导了AP-1转录复合物的激活。我们的研究结果与以下概念一致,即血小板在霍奇金淋巴瘤中霍奇金-里德-斯特恩伯格细胞的播散中起关键作用,主要是在脾脏中,通过增加细胞黏附,从而促进它们在淋巴系统之外的增殖和迁移特性。