Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation

Stefanius, Karoliina; Servage, Kelly A.; Santos, Marcela de Souza; Gray, Hillery F.; Toombs, Jason E.; Chimalapati, Suneeta; Kim, Min S.; Malladi, Venkat S.; Brekken, Rolf A.; Orth, Kim

doi:10.7554/elife.40226

Cited by 76 publications

(60 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that some chemotherapies induce CAFs to start to release more exosomes, which in turn promote pancreatic cancer cell proliferation and drug resistance [89]. Exosomes also play a role as cell transformation initiator in human pancreatic cancer; a recent study reported that pancreatic cancer cell exosomes were involved in malignant cell transformation of NIH/ 3 T3 cells, contrarily, this was impossible on exosomes from healthy pancreatic cells or primary fibroblast cells [90]. Macrophages-delivered exosomes are one of the pancreatic cancers TME components, and they are said to be involved in different PC essential events.…”

Section: Mir-550mentioning

confidence: 99%

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer

et al. 2020

View full text Add to dashboard Cite

At the moment, pancreatic cancer is among the deadliest gastrointestinal diseases, and pancreatic cancer growth is a complex biological process that is based on different kinds of genes. Exosomes are extracellular vesicles containing microRNAs (miRNAs), messenger RNA (mRNA), and proteins, they act as the most prominent mediator of intercellular communication, and they regulate, instruct, and re-educate their surrounding microenvironment and target specific organs. Due to accumulative evidence proved that exosomes are involved in metastasis, cell proliferation, EMT, angiogenesis, and TME of pancreatic cancer, exosomes are crucial potential candidates to detect pancreatic cancer early. This review aims to convey the current understanding of the main functions employed by exosomes in early diagnosis and treatment of pancreatic cancer.

show abstract

Section: Mir-550mentioning

confidence: 99%

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Exosome is a member of EV, with the size of 40-150 nm. It packages the proteins and genetic materials from host cells into lipid bilayer and delivers this cargo to the recipient cells 12,13 . This communicational approach can increase the spreading scope and duration time of the signals.…”

Section: Introductionmentioning

confidence: 99%

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

Zhu

Guo

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFHexos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.

show abstract

“…Pancreatic cancer (PAC) is a devastating metastatic disease that severely threatens the human health [28]. Epidemiological investigation identified that the incidence and mortality of PAC raised year by year all over the world [29,30].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer

Zou

Guo

Wei

et al. 2021

neo

View full text Add to dashboard Cite

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway ana lysis were employed to explore the potential regulato ry relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues wa s higher than that of normal tissues (P < 0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (P < 0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (P < 0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW1990 cells and PANC-1 cells (P < 0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (P < 0.05). The colony formation was notably inhibited in the shCDCA3 group relatively to the shCtrl group in SW1990 cells (P < 0.05). Moreover, the tumor growth was evidently suppressed in shCDCA3 group compared with shCtrl group in vivo (P < 0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.

show abstract

Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation

Cited by 76 publications

References 50 publications

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer

Contact Info

Product

Resources

About