The New General Biological Property of Stem-like Tumor Cells (Part II: Surface Molecules, Which Belongs to Distinctive Groups with Particular Functions, Form a Unique Pattern Characteristic of a Certain Type of Tumor Stem-like Cells)

Abstract

An ability of poorly differentiated cells of different genesis, including tumor stem-like cells (TSCs), to internalize extracellular double-stranded DNA (dsDNA) fragments was revealed in our studies. Using the models of Krebs-2 murine ascites carcinoma and EBV-induced human B-cell lymphoma culture, we demonstrated that dsDNA internalization into the cell consists of several mechanistically distinct phases. The primary contact with cell membrane factors is determined by electrostatic interactions. Firm contacts with cell envelope proteins are then formed, followed by internalization into the cell of the complex formed between the factor and the dsDNA probe bound to it. The key binding sites were found to be the heparin-binding domains, which are constituents of various cell surface proteins of TSCs—either the C1q domain, the collagen-binding domain, or domains of positively charged amino acids. These results imply that the interaction between extracellular dsDNA fragments and the cell, as well as their internalization, took place with the involvement of glycocalyx components (proteoglycans/glycoproteins (PGs/GPs) and glycosylphosphatidylinositol-anchored proteins (GPI-APs)) and the system of scavenger receptors (SRs), which are characteristic of TSCs and form functional clusters of cell surface proteins in TSCs. The key provisions of the concept characterizing the principle of organization of the “group-specific” cell surface factors of TSCs of various geneses were formulated. These factors belong to three protein clusters: GPs/PGs, GIP-APs, and SRs. For TSCs of different tumors, these clusters were found to be represented by different members with homotypic functions corresponding to the general function of the cluster to which they belong.

Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations

“…This study is the first step in creating a new technology for HSC genome reconstruction/equalization based on the discovered ability of poorly differentiated cells, including HSCs, to capture dsDNA by a natural mechanism described in previous studies ( 16 , 17 ). The proposed analysis is the basis for the technological platform for obtaining a primary in situ screenshot of the colony phenotype and genetic changes directly on plates.…”

“…We discovered and described a new general biological property of stem cells of various genesis in our recent studies ( 15 - 17 ). It has been experimentally shown that HSCs, as well as all the analyzed low-differentiated cells of mammals, including tumor-initiating stem cells, are able to capture dsDNA from the environment by a natural mechanism.…”

“…each stem cell has three functional protein domains composed of different representatives of these domains, which determine the interaction of the extracellular dsDNA with the cell and its internalization. The main binding site for dsDNA molecules is the heparin-binding domain (the C1q domain, the collagen-binding domain, and positively charged amino acids) found in various cell surface proteins ( 16 , 17 ).…”

Developmental Biology: Computational and Experimental Approaches

“…This Special Issue entitled “Developmental Biology: Computational and Experimental Approaches” of the International Journal of Molecular Sciences includes six contributions as original articles [ 4 , 5 , 6 , 7 , 8 , 9 ], providing new information about the experimental and computational approaches that promote technical progress for research into developmental biology.…”

“…A study by Petrova et al [ 8 ] provides a molecular-level summary of the results obtained from an eight-year-long research effort in the development of a therapeutic approach named ‘Karanahan’ to treat malignant neoplasms. The study started with an unexpected observation that Krebs-2 mouse ascites tumor cells are capable of internalizing extracellular double-stranded DNA (dsDNA) natively without any special transfection procedures [ 15 ].…”