Peripheral trafficking of bone-marrow-derived stem cells in patients with different types of gastric neoplasms

Abstract

Recently, there has been a growing interest in the importance of stem cells (SCs) in the development/progression of gastric neoplasms. In this study, we performed a comprehensive analysis of different populations of bone-marrow-derived stem cells (BMSCs) in patients with various types of gastric malignancies, including gastric cancer, gastrointestinal stromal tumors (GISTs), neuroendocrine neoplasms (NENs), and lymphomas. We found significantly lower numbers of circulating Lin-/CD45 +/ CD133 + hematopoietic stem/progenitor cells (HSPCs), and intensified peripheral trafficking of both Lin-/CD45-/CXCR4+/CD34+/CD133+ very small embryonic/epiblast-like stem cells (VSELs) and CD105 + /STRO-1 +/ CD45- mesenchymal SCs (MSCs) in patients with gastric cancer, but not in those with other types of gastric neoplasms. No significant differences in the absolute numbers of circulating CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were observed between the groups. This abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was neither associated with clinical stage of the disease nor with systemic levels of stromal-derived factor-1 (SDF-1), as these were comparable to the values observed in control individuals. Interestingly, the absolute numbers of circulating BMSCs correlated with the concentrations of complement cascade-derived anaphylatoxins/molecules (mainly C5b-9/membrane attack complex-MAC) and sphingosine-1-phosphate (S1P). In summary, our translational study revealed that abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Further, our findings indicate that highlighted complement cascade-derived molecules and S1P, but not SDF-1, are significant players associated with this phenomenon.

Interleukins 17 and 23 in patients with gastric neoplasms

“…We found that, in patients with gastric carcinoma, peripheral levels of IL-17 were correlated only with IL-12 concentrations, whereas IL-23 levels were significantly associated with IL-10 values (Table 2). We also performed an analysis of correlations between the examined interleukins and the absolute numbers of circulating BMSCs reported previously21. This analysis demonstrated that systemic levels of IL-23 were negatively correlated with selected populations of BMSCs, mainly very small embryonic/epiblast-like stem cells and mesenchymal stem cells (Table 2).…”

“…This is associated with both the clinical presentation of gastric tumors and with the recently reported phenomenon of intensified peripheral trafficking of selected populations of bone marrow-derived stem cells (BMSCs) in patients with gastric carcinoma21. We additionally posited that measurements of systemic levels of examined interleukins could be of potential diagnostic value in differentiating gastric carcinoma from other types of gastric neoplasms in humans.…”

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

“…Within time, animal and experimental reports confirmed the significance of BMSCs in the pathogenesis of different types of neoplasm developing in various organs, such as the lung, brain, and/or GI tract malignancies [19][20][21]. Further translational evidence confirming the existence of BMSC mobilization toward the developing tumor in humans was provided through a detailed molecular analysis of tumor specimens derived from patients that underwent BM transplantation because of hematological malignancies.…”

“…Interestingly, in our recent studies, we observed an intensified systemic trafficking of BMSCs in patients with gastric and pancreatic cancer. This process did not seem to be associated with the clinical stage of the disease and occurred in patients presenting with both early and advanced disease [21,24].…”

“…For example, as mentioned before, we demonstrated that among various BMSCs, a population of recently discovered small SCs-VSELs-intensively egresses from the BM environment, and increased numbers of these SCs circulate in peripheral blood derived from patients with pancreatic cancer [24]. Currently the concept of VSELs is a matter of a lively debate, because some investigators challenged the existence of such SCs, whereas others provided further reports about the significance of VSELs in regeneration of various organs and cancerogenesis [21,[82][83][84]. Therefore, the eventual role of these BMSCs in pancreatic adenocarcinoma development/progression still needs to be defined and will undoubtedly be intensively examined within upcoming years.…”