title: Fusion-derived epithelial cancer cells express hematopoietic markers and contribute to stem cell and migratory phenotype in ovarian carcinoma.
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.
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Mallika
authors.initials: M
authors.lastname: Ramakrishnan
authors.forename: Sandeep R
authors.initials: SR
authors.lastname: Mathur
authors.forename: Asok
authors.initials: A
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077216:Carcinoma, Ovarian Epithelial; D002454:Cell Differentiation; D002459:Cell Fusion; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D002633:Chemotaxis; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D015415:Biomarkers; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4