Abstract
For a long time, the external milieu of cancer cells was considered to be of secondary importance when compared with its intrinsic properties. That has changed now as the microenvironment is considered to be a major contributing factor toward the progression of tumor. In this study, we show that in human and mouse epithelial ovarian carcinoma and mouse lung carcinoma, the interaction between tumor-infiltrating hematopoietic cells and epithelial cancer cells results in their fusion. Intriguingly, even after the fusion event, cancer cells retain the expression of the pan-hematopoietic marker (CD45) and various markers of hematopoietic lineage, including those of hematopoietic stem cells, indicating that the hematopoietic genome is not completely reprogrammed. This observation may have implications on the bone marrow contribution to the cancer stem cell population. Interestingly, it was seen that in both cancer models, the expression of chemokine receptor CXCR4 was largely contributed to by the fused compartment of cancer cells. We hypothesize that the superior migratory potential gained by the cancer cells due to the fusion helps in its dissemination to various secondary organs upon activation of the CXCR4/CXCL12 axis. We are the first to report the presence of a hemato-epithelial cancer compartment, which contributes to stem cell markers and CXCR4 in epithelial carcinoma. This finding has repercussions on CXCR4-based therapeutics and opens new avenues in discovering novel molecular targets against fusion and metastasis.
Highlights
Tumor is a conglomeration of various subpopulations like cancer stem cells (CSC), metastatic CSCs, proinvasive cells, etc., but how cancer cells achieve this heterogeneity is not deciphered completely
We report the presence of a hemato-epithelial compartment in metastasized human epithelial ovarian carcinoma (EOC), primary and metastasized mouse EOC, and primary Lewis lung carcinoma (LLC)
As a significant number of cancer cells were CD45þ, we investigated its association with other hematopoietic stem cell (HSC) antigens
Summary
Tumor is a conglomeration of various subpopulations like cancer stem cells (CSC), metastatic CSCs, proinvasive cells, etc., but how cancer cells achieve this heterogeneity is not deciphered completely. Apart from the intrinsic genetic factors, it is recognized that the tumor microenvironment has a pivotal role in determining the events in carcinogenesis and metastasis [1,2,3,4]. All solid tumors with or without chronic inflammation as a risk factor have a significant component of bone marrow-derived cells Chemical carcinogenesis of mouse BMDCs has been shown to give rise to epithelial, neural, muscular, endothelial, and fibroblastic tumors [6]. Similar observation of donor-derived solid tumors has been made in patients who have undergone bone marrow transplantation
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