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Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells. | LitMetric

AI Article Synopsis

  • The 'cancer cell fusion' theory explores how hybrid cells may contribute to tumor development and metastasis, though identifying these cells has been challenging.
  • Researchers co-cultured lung cancer stem cells with human monocytes to study the characteristics and behavior of tumor-hybrid cells (THCs) through various advanced techniques.
  • Findings indicate that THCs are influenced by the expression of specific markers and the environment of monocytes, allowing them to proliferate and spread, which could lead to new treatments for lung cancer metastasis.

Article Abstract

The 'cancer cell fusion' theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36CD14PANK allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458638PMC
http://dx.doi.org/10.1080/2162402X.2020.1773204DOI Listing

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