Association of VLA4, 5, 6 and PSGL1 expression levels with engraftment in autologous HPSC transplantation in multiple myeloma patients.

The most promising therapy for leukemia is hematopoietic stem cell transplantation. Engraftment of HPSCs mainly depends on some factors such as adhesion molecules, including VLAs. This study tried to delineate the relationship between HPSCs engraftment and expression level of PSGL1 and VLA4, 5, and 6 genes in candidate MM patients for autologous bone marrow transplantation. Firstly, the CD 34+ HPSCs were collected from multiple myeloma (MM) patients after five days of G-CSF therapy through apheresis processes. Then, the patients were categorized into two groups of good and bad prognosis depending on engraftment time (Less or more than 18 days). Followingly, the expression of PSGL1 and VLA4, VLA5, and VLA6 genes were assessed by the qRT-PCR technique in each patient. Finally, the correlation between the genes and engraftment time was investigated to determine the prognostic role of each gene on HPSCs transplantation. Our findings demonstrated that there is a significant correlation between VLA4 (P=< 0.0001) and 5 (P = 0.005) levels and HPSCs engraftment time. As the higher levels of VLA4 and 5, the shorter time HPSCs engraftment occurs. In contrast, there was no significant correlation between VLA6 (P = 0.2) and PSGL1 (P = 0.3) genes levels and engraftment time. So that, the patients with a good prognosis had a higher level of VLA4 and VLA5, but no relation was found between VLA6 and PSGL1. It is concluded that VLA4 and VLA5 expression could be considered a significant prognostic factor for HPSC transplantation.

Gastric cancer increases transmigratory potential of peripheral blood monocytes by upregulation of ß1- and ß2-integrins.

INTRODUCTION: Immune responses within the tumor depend on the ability of leukocytes to migrate from peripheral circulation into the local microenvironment. This process is controlled by mechanisms that guide leukocytes to the side of inflammation, allowing them to cross vascular endothelial barrier. Monocytes/macrophages are the predominant population of leukocyte infiltrate of many tumors, including, gastric cancer. However, to date mechanisms that control monocyte trafficking to the side of tumor growth are not fully elucidated. AIM OF THE STUDY: It this study we aimed to evaluate transmigratory potential of peripheral blood monocytes from gastric cancer patients. MATERIAL AND METHODS: By using multicolor flow cytometry we assessed expression of ß1- and ß2-integrins on peripheral blood monocytes from gastric cancer patients. RESULTS: We found increased frequencies of VLA-4 and VLA-6 expressing monocytes and increased expression of analyzed ß2-integrins in gastric cancer patients when compared to age matched controls. CONCLUSIONS: In summary, this study revealed that gastric cancer increases transmigratory potential of peripheral blood monocytes.

Integrin VLA-6 (α6ß1) is transiently expressed during the development of mouse bone marrow-derived mast cells.

In the present study the involvement of VLA-6 (α6ß1) integrin, a laminin receptor, was characterized during the course of mouse bone marrow-derived mast cell (BMMC) development. Flow cytometry and immunoprecipitation revealed increases in α6 integrin expression during the first 3 weeks, followed by a decline, such that α6ß1 was no longer detectable by week 13. Using RT-PCR, transcripts for α6A but not the α6B isoform were detected. Results from immunoprecipitation and costaining with ß1-or ß4-specific mAb showed the expression of VLA-6 (α6ß1) and not α6ß4 heterodimers. Moreover, the ability of BMMC to interact with laminin correlated with the time period of VLA-6 expression. However, only 40% of adhesion to laminin was inhibited by blocking mAb for α6, indicating the involvement of additional laminin receptor(s). This is supported by the immunoprecipitation of VLA-2 integrin, also known to have laminin binding properties. Heterogeneity of VLA-6 expression was also found in connective tissue-type mast cells; thus, VLA-6hi and VLA-6lo subpopulations of peritoneal mast cells were observed. The heterogeneity of VLA-6 integrin expression in BMMC and CTMC may be relevant to the concept of mast cell heterogeneity as well as to the ability of mast cell precursors to migrate and complete their course of maturation within tissues.

Involvement of VLA-5 and VLA-6 in facilitating endothelium-oriented transmigration of hematopoietic stem/progenitor cells / 吉林大学学报(医学版)

Objective:To investigate whether VLA-5 and VLA-6 are involved in facilitating en-dothelium-oriented transmigration of hematopoietic stem/progenitor cells. Methods:Purified hu-man CD34+ cells were subject to ex vivo transmigration assay and blocking experiments throughtranswell filter inserts coated with human umbilical vein endothelial cells (HUVECs). Four-colorfluorescence-activated cell sorting (FACS) analysis was applied to detect the expression profilesof adhesion molecules and chemokine receptor CXCR-4 on CD34bright cells. Results:Stromal cell-derived factor (SDF)-1-induced transmigrations of both mobilized peripheral blood (mPB)-(56.6±20. 1)% and bone marrow (BM)- (15. 6±1. 8)% derived CD34+ cells were significantlyfacilitated through HUVECs-coated transwell filter insters compared with noncoated ones, whichwere efficiently blocked by preincubation of CD34+ cells with neutralizing antibodies to VLA-5,or VLA-6, or both of them; meanwhile the proportions of migrating CD34+ cells through bothHUVECs-coated and noncoated transwell filter inserts in BM were significantly lower than thosein mPB; the different percentages of migrating CD34+ cells between in mPB and BM were corre-lated with their variable expressions of VLA-5 and VLA-6, but not for VLA-4 or chemokine re-ceptor CXCR-4. Conclusion:Facilitating HS/PCs transmigrations through HUVECs are involvedin both VLA-5 and VLA-6.