Immunization against leukemia inhibitory factor and its receptor suppresses tumor formation of breast cancer initiating cells in BALB/c mouse

• Published in: Scientific reports 2020-07, Vol.10 (1), p.11465-11, Article 11465
• Main Authors: Ghanei, Zahra, Mehri, Nahid, Jamshidizad, Abbas, Joupari, Morteza Daliri, Shamsara, Mehdi
• Format: Article
• Language: English
• Subjects: 631/67/1059/2325; 631/67/1347; Animals; Antigens; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer; Disease Models, Animal; E coli; Female; Growth Inhibitors - immunology; Humanities and Social Sciences; Humans; Immunization; Immunotherapy; Inoculation; Interleukin 2; Interleukin-6 - genetics; Leukemia; Leukemia inhibitory factor; Leukemia Inhibitory Factor - genetics; Leukemia Inhibitory Factor - immunology; Mice; multidisciplinary; Neoplastic Stem Cells - immunology; Protein Binding - genetics; Receptors, OSM-LIF - genetics; Receptors, OSM-LIF - immunology; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Tumors; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68158-0

Immunotherapy is a promising approach for specific targeting of cancer cells. Leukemia inhibitory factor (LIF) regulates several features of cancers and cancer stem cells (CSCs) through binding to LIF receptor (LIFR). In this study, we investigated the consensus of LIF and LIFR immunization on the growth of mouse mammary tumors. For this purpose, mouse LIF and LIFR were designed as truncated proteins, expressed in E. coli and then injected to mice as individual and mixed antigens. The results showed the production of neutralizing antibodies and secretion of interferon-γ and interleukin-2 in response to immunization. In continue, the immunized mice were subjected for tumor formation challenge by inoculation of the breast CSCs derived from MC4-L2 cells. Development of the breast tumors was observed in all the control mice, while the tumors appeared in 75% of animals in the LIF group. LIFR injection, individually or in combination with LIF, strongly inhibited the tumor growth to only 25% of the mice. Moreover, a delay in tumor appearance was observed in the immunized mice compared to the controls. Immunostaining of the tumor sections confirmed the expression of LIF and LIFR. In conclusion, LIF and LIFR might be effective targets for immunotherapy of the tumors that express these proteins.