Breast tumor cell hybrids form spontaneously in vivo and contribute to breast tumor metastases
| Autor: | Tanner J. McArdle, Claire Dietzsch, Brenda M. Ogle, Brian T. Freeman, Felicite K. Noubissi, Casey A Chitwood, Gabriel Jacobs, Annanya Banga |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Medical technology lcsh:Biotechnology Cell Biomedical Engineering Biophysics Cre recombinase Bioengineering Invited Articles Biology Metastasis Biomaterials 03 medical and health sciences 0302 clinical medicine In vivo lcsh:TP248.13-248.65 medicine Mammary tumor Cancer medicine.disease Primary tumor 030104 developmental biology medicine.anatomical_structure lcsh:R855-855.5 Special Topic: Bioengineering of Cancer 030220 oncology & carcinogenesis Cancer cell Cancer research |
| Zdroj: | APL Bioengineering, Vol 2, Iss 3, Pp 031907-031907-19 (2018) APL Bioengineering |
| ISSN: | 2473-2877 |
| DOI: | 10.1063/1.5024744 |
| Popis: | Cancer cell fusion was suggested as a mechanism of metastasis about a century ago. Since then, many additional modes of material transfer (i.e., tunneling nanotubes, and exosomes) to generate cell hybrids have been identified. However, studies documenting spontaneous tumor hybrid formation in vivo as a mechanism that enables metastasis are still lacking. Here, we tested whether spontaneous hybrid formation in vivo contributes to bona fide metastatic tumors. We first used single cell RNASeq to analyze the gene expression profile of spontaneously formed cancer cell-stromal hybrids, and results revealed that hybrids exhibit a clustering pattern that is distinct from either parental cell and suggestive of substantial diversity of individual hybrids. Despite the newly gained diversity, hybrids can retain expression of critical genes of each parental cell. To assess the biological impact of cancer cell hybrids in vivo, we transfected murine mammary tumor cells, isolated from FVB/N-Tg(MMTV-PyVT)634Mul/J mice (PyVT) with Cre recombinase prior to injection to the murine fat pad of FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J mice such that luciferase expression is induced with hybrid formation; luciferase expression was tracked for up to four months. We observed that hybrid formation occurs spontaneously in vivo and that a significantly higher number of hybrids reside in metastases compared to the primary tumor, supporting the possibility that hybrids can emerge from the primary tumor and proliferate to help create a new tumor at a distant site. Additional studies are now warranted to delineate the mechanisms of cancer cell hybrid transit to metastases since drugs to inhibit hybrid formation might prevent metastatic spread. |
| Databáze: | OpenAIRE |
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