bims-stacyt 2021-05-30 papers

Biotech Histochem. 2021 May 28. 1-12

Possible role of WNT10B in increased proliferation and tubule formation of human umbilical vein endothelial cell cultures treated with hypoxic conditioned medium from human adipocytes.

Sara Pourdashti, Nassim Faridi, Hamid Yaghooti, Mohammad-Taha Jalali, Ahmadreza Soroush, S Zahra Bathaie.

Regulation of angiogenesis plays an important role in adipose tissue expansion and function. The Wnt pathway and WNT10B, the main member of Wnt family, participate in angiogenesis in cancer tumors, but there is limited evidence to support the regulatory role of WNT10B in human adipose tissue angiogenesis. Subcutaneous white adipose tissue (scWAT) of 80 participants including obese and non-obese subjects was obtained and the expression of WNT10B and VEGFA genes were evaluated using qPCR. Human adipose-derived stem cells (hADSC) were differentiated to adipocytes and incubated under either hypoxic or normoxic conditions. The conditioned media of these adipocytes were collected and used as growth media for human umbilical vein endothelial cells (HUVEC) in Matrigel. We evaluated the proliferation, cell cycle phases, tubule formation and β-catenin activation of these treated cells. We found a significant correlation between WNT10B and VEGFA expression in the scWAT of both obese and non-obese subjects. Proliferation and tubule formation of HUVEC treated with conditioned media of hypoxic adipocytes (hCM) in the S-phase were increased significantly compared to the HUVEC treated with the conditioned media of normoxic adipocytes (nCM). The expression of WNT10B and VEGFA was enhanced in hypoxic adipocytes compared to normoxic adipocytes; also, activation and nuclear translocation of β-catenin was enhanced in the HUVEC treated with hCM compared to nCM. WNT10B acts as an angiogenic protein in scWAT under hypoxic conditions. Hypoxia induced WNT10B increases VEGFA expression and causes tube formation by HUVECs and angiogenesis in adipose tissue via the canonical Wnt/β-catenin pathway.

Keywords: Adipose tissue; VEGFA; WNT10B; angiogenesis; conditioned medium; human; hypoxia; normoxia; umbilical vein; β-catenin

DOI: https://doi.org/10.1080/10520295.2021.1923801

Eur J Obstet Gynecol Reprod Biol. 2021 May 11. pii: S0301-2115(21)00234-7. [Epub ahead of print]262 174-181

Conditioned medium derived from seminal extracellular vesicles-exposed endometrial stromal cells induces inflammatory cytokine secretion by macrophages.

Shahrokh Paktinat, Sahar Esfandyari, Amin Karamian, Ameneh Koochaki, Ali Asadirad, Marefat Ghaffari Novin, Samira Mohammadi-Yeganeh, Saghar Salehpour, Seyed Mahmoud Hashemi, Hamid Nazarian.

OBJECTIVE: Seminal plasma (SP) contains large numbers of sub-cellular structures called extracellular vesicles (EV) which have been postulated to have immunological functions due to their bioactive contents including proteins and small non-coding RNAs. Although the response of endometrial cells to seminal EV (SEV) is recently being elucidated, the impact of these signaling vesicles on stroma-immune crosstalk is still unknown. Herein, we aimed to investigate the effect of conditioned medium (CM) derived from SEV-exposed endometrial stromal cells (eSC) on cytokine secretion by macrophages.
STUDY DESIGN: SEV were isolated from SP samples of healthy donors and characterized by common methods needed for EV characterization, including size determination by dynamic light scattering (DLS), transmission electron microscopy (TEM), and western blot analysis of EV markers. Endometrial biopsies were obtained from healthy individuals and eSC were isolated and characterized. EV internalization assay was performed by labeling the SEV with PKH67 green fluorescent dye. Then, the eSC were exposed to SEV and the CM was collected. Finally, the CM from SEV-exposed eSC was added to the macrophage culture and the level of inflammatory (interleukin (IL)-1α and IL-6) and anti-inflammatory (IL-10) cytokines were measured in the culture supernatant of macrophages.
RESULTS: The results demonstrated that the CM derived from SEV-exposed eSC induce IL-1α and IL-6 secretion by the macrophages, while the secretion of IL-10 was reduced.
CONCLUSION: Our results support the idea that the stroma-immune interaction is affected by SEV. This effect may be a part of immunoregulatory function of SP inside upper female genital tract and have an obvious impact during peri-implantation period.

Keywords: Endometrium; Extracellular vesicles; Macrophages; Semen; Stromal cells

DOI: https://doi.org/10.1016/j.ejogrb.2021.05.019

Cancer Res. 2021 May 28. pii: canres.3929.2020. [Epub ahead of print]

Apolipoprotein E promotes immune suppression in pancreatic cancer through NF-kB-mediated production of CXCL1.

Samantha B Kemp, Eileen S Carpenter, Nina G Steele, Katelyn L Donahue, Zeribe Chike Nwosu, Amanda Pacheco, Ashley Velez-Delgado, Rosa E Menjivar, Fatima Lima, Stephanie The, Carlos E Espinoza, Kristee Brown, Daniel Long, Costas A Lyssiotis, Arvind Rao, Yaqing Zhang, Marina Pasca di Magliano, Howard C Crawford.

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with few effective therapeutic options. PDA is characterized by an extensive fibroinflammatory stroma that includes abundant infiltrating immune cells. Tumor-associated macrophages (TAM) are prevalent within the stroma and are key drivers of immunosuppression. TAMs in human and murine PDA are characterized by elevated expression of apolipoprotein E (ApoE), an apolipoprotein that mediates cholesterol metabolism and has known roles in cardiovascular and Alzheimer's disease but no known role in PDA. We report here that ApoE is also elevated in peripheral blood monocytes in PDA patients, and plasma ApoE protein levels stratify patient survival. Orthotopic implantation of mouse PDA cells into syngeneic wild-type or in ApoE-/- mice showed reduced tumor growth in ApoE-/- mice. Histological and mass cytometric (CyTOF) analysis of these tumors showed an increase in CD8+ T cells in tumors in ApoE-/- mice. Mechanistically, ApoE induced pancreatic tumor cell expression of Cxcl1 and Cxcl5, known immunosuppressive factors, through LDL receptor and NF-kB signaling. Taken together, this study reveals a novel immunosuppressive role of ApoE in the PDA microenvironment.

DOI: https://doi.org/10.1158/0008-5472.CAN-20-3929