Dataset Information

Tumor-Derived Exosomal CCT6A Serves as a Matchmaker Introducing Chemokines to Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma

ABSTRACT: M2-polarized tumor-associated macrophages (TAMs) are a key factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). While various factors within the tumor microenvironment drive their formation, the role of PDAC-derived exosomes in this process remains unclear. We aim to clarify the regulatory impacts of tumor-derived exosomes to TAMs. Through multi-Omics analysis, we identified CCT6A as a novel tumor-derived exosomal protein, bridging TAMs M2 polarization and PDAC prognosis. Co-culture with exosomes derived from CCT6Ahigh PDAC leads to greater M2 phenotype of TAMs via PI3K-AKT signaling. According to proteomics data, chemokines’ abundance reduces over tenfold once exosomal CCT6A absence, including CXCL1, CXCL3, CXCL20 and CCL5, whose interaction with CCT6A in PDAC cells was confirmed by interactomics data. Morever, we found CCT6A clearance abrogated the antagonism effects of CD47 antibody immunotherapy. The subunit of the T-complex protein Ring Complex (TRiC) CCT6A serves as a matchmaker, during exosomes-mediated chemokines transfer from PDAC to TAMs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Neoplastic Cell

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Minghe Zhang

LAB HEAD: Yuan Yufeng

PROVIDER: PXD056403 | Pride | 2025-05-26

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2_MWY-24-1040-01-a_DIA_human_666a_Slot1-33_1_11222.d.zip	Other
	2_MWY-24-1040-01-a_DIA_human_667a_Slot1-34_1_11223.d.zip	Other
	2_MWY-24-1040-01-a_DIA_human_668a_Slot1-35_1_11224.d.zip	Other
	2_MWY-24-1040-01-a_DIA_human_669a_Slot1-36_1_11225.d.zip	Other
	2_MWY-24-1040-01-a_DIA_human_670a_Slot1-37_1_11226.d.zip	Other

Items per page:

1 - 5 of 14

Publications

Tumor-derived exosomal CCT6A serves as a matchmaker introducing chemokines to tumor-associated macrophages in pancreatic ductal adenocarcinoma.

Ma Tianyin T Guo Wing-Wa WW Zhang Minghe M He Wenzhi W Dongzhi Cairang C Gongye Xiangdong X Xia Peng P Chai Yibo Y Chen Zhang Z Zhu Yimin Y Qu Chengming C Liu Jie J Yang Zhiyong Z Ma Weijie W Tian Ming M Yuan Yufeng Y

Cell death & disease 20250515 1

M2-polarized tumor-associated macrophages (TAMs) are a key factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). While various factors within the tumor microenvironment (TME) drive their formation, the role of PDAC-derived exosomes in this process remains unclear. We aim to clarify the regulatory impacts of tumor-derived exosomes to TAMs. After the intratumoral injection to subcutaneous tumor of C57BL/6 mice, we demonstrated PDAC-derived exosomes exacerbate PDAC p ...[more]

PMID: 40374617

Similar Datasets

Project description:In vitro maturation (IVM) of oocytes retrieved from ovum pick-up (OPU) or ovarian tissue (OT) is a standard approach for patients with specific conditions where prior hormonal stimulation is contraindicated. However, the developmental competence of oocytes matured in vitro is still inferior to that of oocytes matured in vivo. Capacitation-IVM (CAPA-IVM) includes an extra step of pre-maturation culture (PMC) with c-type natriuretic peptide (CNP) as a meiotic arrestor to better synchronize cytoplasmic and nuclear maturity in oocytes. This study aims to evaluate the effect of CAPA-IVM on equine oocyte quality and developmental competence. Immature cumulus-oocyte complexes (COCs) were retrieved from slaughterhouse ovaries and matured in vitro either in CAPA-IVM (short or long) or standard IVM. Matured oocytes from each group were analyzed for calcium-releasing potential and single-oocyte proteomics, and embryo development was assessed after fertilization with Piezo-drilled intracytoplasmic sperm injection (ICSI). Genetic analysis of developed blastocysts was performed to detect chromosomal aberrations. Our findings demonstrate that CAPA-IVM of equine COCs yields significantly higher maturation rates than controls. Moreover, short CAPA-IVM with six hours pre-maturation culture showed substantially higher embryo development potential than the control group. Genetic analysis revealed a high euploidy rate in equine blastocysts regardless of the maturation conditions. Live calcium imaging of the fertilized oocytes demonstrated the majority of oocytes with non-continuous calcium oscillation patterns, irrespective of maturation conditions. Single oocyte proteomics reveals a comparable proteomic landscape between matured oocytes from short CAPA-IVM and standard IVM. However, a trend of differential expression was observed in specific proteins related to cytoskeleton, cell cycle, and hemostasis in the short CAPA-IVM group. Our findings indicate that CAPA-IVM holds the potential to improve oocyte quality and competence in horses. However, further fine-tuning of culture conditions based on omics analysis would benefit the effective use of these IVM systems. Moreover, given that the mare serves as an excellent model for human reproduction, the molecular trends identified in this study could provide valuable insights for advancing human artificial reproductive technologies.

Project description:Oral transmission of T. cruzi is probably the most frequent mechanism among animals in the wild. In this context, there is a high prevalence of human infections in regions where triatomine infection with T. cruzi is low. This led to the hypothesis that the consumption of raw or undercooked meat from animals infected with T. cruzi could be responsible for the transmission of the infection. Therefore, the general objective of this study was to demonstrate the role of meat consumption from infected animals in the oral transmission of T. cruzi infection. Groups of five female mice Balb/c were fed with muscles obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacity. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies. In all cases, 60–100% of animals were fed meat from mice infected in the acute phase or infected by means of a nasogastric probe with trypomastigotes or amastigotes. These animals developed high parasitemia, and 80% died around day 40 post-infection. The adhesion tests showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS also confirmed that transialidase may be involved in TCT attachment of TCT or invasion of stomach cells. It was concluded that the consumption of meat from infected animals in the acute phase of T. cruzi infection allows transmission of the infection. Similarly, trypomastigotes and amastigotes were able to infect mice when administered orally, while cruzipain was a relevant molecule in this infective process.