The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells.

in Frontiers in genetics by Genrikh S Ritter, Evgeniya V Dolgova, Daria D Petrova, Yaroslav R Efremov, Anastasia S Proskurina, Ekaterina A Potter, Vera S Ruzanova, Svetlana S Kirikovich, Evgeniy V Levites, Oleg S Taranov, Alexandr A Ostanin, Elena R Chernykh, Nikolay A Kolchanov, Sergey S Bogachev

TLDR

  • The study investigates how stem-like tumor cells from certain types of cancer can take in DNA from their surroundings. The study found that these cells have a positive charge on their surface that helps them bind and internalize the DNA. This could have important implications for cancer treatment and diagnosis, as it suggests that these cells could be targeted for therapy or used as biomarkers for cancer diagnosis. The study also identified the role of scavenger receptors in the internalization process, which could be exploited for drug delivery or targeted therapy. Overall, the study provides important insights into the mechanisms underlying the uptake of DNA in stem-like tumor cells and its potential implications for cancer treatment and diagnosis.

Abstract

Stem-like tumor cells of ascites carcinoma Krebs-2 and Epstein-Barr virus-induced B-lymphoma were shown to possess the innate capability of binding and internalizing the TAMRA-labeled double-stranded DNA (dsDNA) probe. The process of binding and internalizing is rather complicated and composed of the following successive stages: 1) initiating electrostatic interaction and contact of a negatively charged dsDNA molecule with a positively charged molecule(s) on the surface of a stem-like tumor cell; 2) binding of the dsDNA probe to a tumor stem cell surface protein(s)the formation of a strong chemical/molecular bond; and 3) the very internalization of dsDNA into the cell. Binding of DNA to cell surface proteins is determined by the presence of heparin/polyanion-binding sites within the protein structure, which can be competitively blocked by heparin and/or dextran sulfate, wherein heparin blocks only the binding, while dextran sulfate abrogates both binding and internalization. The abrogation of internalization by dextran sulfate implies the role of scavenger receptors in this process. Cells were shown to uptake DNA in amounts constituting ∼0.008% of the haploid genome. Inhibitors of caveolae-dependent internalization abrogate the DNA uptake in Krebs-2 cells, and inhibitors of the clathrin/caveolar mechanism block the internalization in B-lymphoma cells. In the present report, it is shown for the first time that in contrast to the majority of committed tumor cells, stem-like tumor cells of Krebs-2 and B-lymphoma carry a general positive charge on their surface.

Overview

  • The study investigates the ability of stem-like tumor cells from ascites carcinoma Krebs-2 and Epstein-Barr virus-induced B-lymphoma to bind and internalize a TAMRA-labeled dsDNA probe. The process involves three stages: initiating electrostatic interaction, binding to cell surface proteins, and internalization. The study finds that stem-like tumor cells carry a general positive charge on their surface, which facilitates the binding and internalization of dsDNA. The study aims to understand the mechanisms underlying the uptake of DNA in stem-like tumor cells and its potential implications for cancer treatment and diagnosis.

Comparative Analysis & Findings

  • The study compares the uptake of dsDNA in stem-like tumor cells from Krebs-2 and B-lymphoma. The results show that stem-like tumor cells from both cell lines possess the ability to bind and internalize dsDNA. The study also identifies the role of scavenger receptors in the internalization process. The key findings of the study are that stem-like tumor cells carry a general positive charge on their surface, which facilitates the binding and internalization of dsDNA. The study also shows that the uptake of dsDNA in stem-like tumor cells is constitutive and independent of the cell type.

Implications and Future Directions

  • The study's findings have significant implications for cancer treatment and diagnosis. The ability of stem-like tumor cells to bind and internalize dsDNA suggests that they may be targeted for therapy or used as biomarkers for cancer diagnosis. The study also identifies the role of scavenger receptors in the internalization process, which may be exploited for drug delivery or targeted therapy. Future research directions could include investigating the specific proteins involved in the binding and internalization of dsDNA in stem-like tumor cells, exploring the role of stem-like tumor cells in cancer progression and metastasis, and developing targeted therapies based on the findings of this study.
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