Abstract
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.
Highlights
Immunotherapy is a promising approach for specific targeting of cancer cells
The rtLIFR in length of 180 amino acids was a part of mouse LIF receptor (LIFR) protein bearing D3 and D4 domains (Sequence of both proteins is presented in supplementary data)
The stability of both protein transcripts was calculated by the Mfold web server to be -106.68 for recombinant truncated LIF (rtLIF) and-139.39 kcal/mol for rtLIFR
Summary
Leukemia inhibitory factor (LIF) regulates several features of cancers and cancer stem cells (CSCs) through binding to LIF receptor (LIFR). 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 injected to mice as individual and mixed antigens. LIFR injection, individually or in combination with LIF, strongly inhibited the tumor growth to only 25% of the mice. Leukemia inhibitory factor (LIF) is a pleiotropic protein belonging to the interleukin-6 family cytokines It is a highly conserved secretory glycoprotein among different species. It seems that inhibition of LIF and LIFR might be a therapeutic strategy in suppression of these kind of cells
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