Forskningsbeskrivning
Cell fusion is a common physiological process that results in viable cells and plays a significant role in mammalian development and differentiation. Somatic cells acquire nuclear reprogramming and epigenetic modifications through cell fusion to form pluripotent hybrid cells. Thus, cell fusion is an efficient process of rapid phenotypic and functional evolution that generates cells with new properties at a rate exceeding that achievable by random mutagenesis. Comprehensive in vitro, in vivo and clinical evidence indicates that cell fusion does occur in solid tumors and contributes to cancer progression. Cell fusion generates progeny that expresses stem-like traits and features of epithelial-mesenchymal transition, which facilitates tumor migration and invasion, constituting an attractive mechanism to explain the process of metastasis. Moreover, these hybrids may acquire resistance to the oncologic treatments the parent cells were sensitive to and result in clonogenic dormant cells contributing to tumor recurrence. These outcomes have been demonstrated for both irradiation and chemotherapy, making cell fusion a potential mechanism contributing to treatment resistance and disease relapse.
Tumor-associated macrophages constitute a major cellular component of the innate immune system in solid tumors. Fusion is an essential function of macrophages, as they, for example, fuse to generate osteoclasts and inflammatory giant cells. Macrophages constitute an important fusion partner to neoplastic cells, developing hybrids that acquire increased metastatic potential and express macrophage-specific phenotype, such as the M2-macrophage-specific marker CD163. Hence, based on cell fusion theory, macrophage traits in cancer cells are suggested to be due to the fusion between tumor cells and macrophages, and CD163 constitutes a surrogate marker to detect macrophage/cancer cell fusion events. The fusion events are rare but increase dramatically (10-100 folds higher) in pathological conditions such as tissue injury, inflammation, hypoxia and apoptosis. Inflammation is a hallmark of cancer and thus constitutes a promoting environment for cell fusion in solid tumors.
Ongoing projects
- Biological and clinical significance of macrophages and cell fusion in breast cancer - retrospective clinical studies.
- Impact of ionizing radiation on cell fusion and development of radio-resistance in cancer cells
- The clinical significance of tumor-microenvironment and de-differentiation in papillary thyroid cancer
- Morphometric analysis and application of artificial intelligence in solid tumors
Selected publications
- Shabo I, Midtbö K, Andersson H, Åkerlund E, Olsson H, Wegman P, Gunnarsson C, Lindström A. Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction. BMC Cancer. 2015 Nov 20;15:922. doi: 10.1186/s12885-015-1935-0.
- Lindström A, Midtbö K, Arnesson LG, Garvin S, Shabo I. Fusion between M2-macrophages and cancer cells results in a subpopulation of radioresistant cells with enhanced DNA-repair capacity. Oncotarget. 2017 May 18;8(31):51370-51386. doi: 10.18632/oncotarget.17986.
- Shabo I, Svanvik J, Lindström A, Lechertier T, Trabulo S, Hulit J, Sparey T, Pawelek. Roles of cell fusion, hybridization and polyploid cell formation in cancer metastasis. J.World J Clin Oncol. 2020 Mar 24;11(3):121-135. doi: 10.5306/wjco.v11.i3.121.
- Shabo I, Stål O, Olsson H, Doré S, Svanvik J. Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer. 2008 Aug 15;123(4):780-6. doi: 10.1002/ijc.23527.
- Shabo I, Olsson H, Sun XF, Svanvik J. Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time. Int J Cancer. 2008 Aug 15;123(4):780-6. doi: 10.1002/ijc.23527.
- Shabo I, Olsson H, Stål O, Svanvik J. Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival. Clin Breast Cancer. 2013 Oct;13(5):371-7. doi: 10.1016/j.clbc.2013.05.003.
- Aljabery F, Olsson H, Gimm O, Jahnson S, Shabo I. M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer. Urol Oncol. 2018 Apr;36(4):159.e19-159.e26. doi: 10.1016/j.urolonc.2017.11.020.
- Aljabery F, Shabo I, Saudi A, Holmbom M, Olson H, Jahnson S. The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer. Urol Oncol. 2023 Mar;41(3):148.e9-148.e16. doi: 10.1016/j.urolonc.2022.12.005.