Pedf derived peptides affect colorectal cancer cell lines resistance and tumour re-growth capacity

Honrubia-Gómez, Paloma; López-Garrido, María-Pilar; Gil-Gas, Carmen; Sánchez-Sánchez, José; Alvarez-Simón, Carmen Belen; Cuenca-Escalona, Jorge; Perez, Ana Ferrer; Arias, Enrique; Moreno, Raul Alejandro Andrade; Sánchez-Sánchez, Francisco; Ramírez-Castillejo, Carmen

doi:10.18632/oncotarget.26085

Cited by 6 publications

(19 citation statements)

References 48 publications

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“…The back regulator and signaling involved need to be further identified through high-throughput sequencing. PEDF was widely considered as a tumor suppressor in solid tumors as it exhibits antiangiogenic and antimetastatic activities ( Baxter-Holland and Dass, 2018 ; Nardi et al, 2018 ; Ansari et al, 2019 ; Honrubia-Gomez et al, 2019 ; Huang et al, 2019 ). Its role in hematologic malignancies such as leukemia, lymphoma, and multiple myeloma remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The m6A Methyltransferase METTL3 Is Functionally Implicated in DLBCL Development by Regulating m6A Modification in PEDF

Cheng

Wang

et al. 2020

Front. Genet.

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Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, whose treatment still has a major challenge of achieving a satisfactory curative effect. The underlying mechanisms also have not been fully illustrated. N 6-Methyladenosine (m6A) has been identified as the most prevalent internal modification of mRNAs present in eukaryotes, which is involved in the pathogenesis of cancers. It remains unclear how m6A mRNA methylation is functionally linked to the pathogenesis of DLBCL. In this study, we sought to explore the roles of METTL3 on DLBCL development. The results showed that m6A level for RNA methylation and the expression level of METTL3 were upregulated in DLBCL tissues and cell lines. Functionally, downregulated METTL3 expression in DLBCL cells inhibited the cell proliferation ability. Further mechanism analysis indicated that METTL3 knockdown abates the m6A methylation and total mRNA level of pigment epithelium-derived factor (PEDF). However, Wnt/β-catenin signaling was not thus activated. Overexpressed PEDF abrogates the inhibition of cell proliferation in DLBCL cells that is caused by METTL3 silence. In summary, the abovementioned results demonstrated that the METTL3 promotes DLBCL progression by regulating the m6A level of PEDF.

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Section: Discussionmentioning

confidence: 99%

The m6A Methyltransferase METTL3 Is Functionally Implicated in DLBCL Development by Regulating m6A Modification in PEDF

Cheng

Wang

et al. 2020

Front. Genet.

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“…In this scenario, we have addressed the problem of locating breast tumour-initiating cells, and the study of the self-renewal mechanism by inhibiting its functionality and potential tumour recurrence. We also postulate that the PEDF signalling pathway could be a potential therapeutic target for control of cancer initiating cells' self-renewal and tumour relapse, as has been postulated in other neoplastic models [30].…”

Section: Introductionmentioning

confidence: 55%

“…This method [30] is used to quantify surviving cells. 5 000 cells/well were seeded in 24-well plates, in a final volume of 250 µL.…”

Section: Methyl Purple Assaymentioning

confidence: 99%

Moonlighting Role of PEDF in Breast Cancer

Gil-Gas

Sánchez‐Díez

Honrubia-Gómez

et al. 2020

Preprint

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Background: Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies has increased the probability of remission, relapse rates still remain high. Numerous studies have indicated the connection between cancer initiating cells and slow cellular cycle cells, identified by their capacity to retain long labelling (LT+). Methods: We have designed a transgenic protein consisting in the C-terminal part of this protein, which acts by blocking endogenous PEDF in culture cell assays. Present work is based in doses-response in vitro assays as well as flow cytometry analysis of surface markers and cell cycle kinetic study of the tumour initiating cells.Results: In this study we show that this type of cells is present not only in cancer cell lines but also in cancer cells from patients with metastatic and advanced stage tumours. We also present new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, expression of markers, and carcinogenicity of cancer stem cells. This protein has been involved in self-renewal in adult stem cells and has been described as anti-tumoral because of its anti-angiogenic effect. However, we show that PEDF enhances resistance in breast cancer patient cells in vitro culture by favoring a slow cellular cycle population (LT+). The PEDF signalling pathway could be a useful tool for controlling cancer stem cells self-renewal, and therefore control patient relapse. Conclusions: We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against Docetaxel treatment in cancer patient cells in vitro culture. We have also demonstrated that this PEDF modified protein produces a significant decrease in cancer stem cell markers. All these properties make this protein a potential application in clinical cancer therapies via co-administration with chemotherapy for relapse cancer treatment.

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Section: Introductionmentioning

confidence: 72%

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

Gil-Gas,

Sánchez-Díez,

Honrubia-Gómez

et al. 2023

Preprint

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Background: Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies has increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer initiating cells and slow cellular cycle cells, identified by their capacity to retain long labelling (LT+). Methods: In this study, we perform tumour cell culture dose-response assays in adherent and mamospheres cultures. We also probe our conclusion in Xenograft models. Cell culture and in vivo tumours were analysed by immunofluorescence, qPCR and flow cytometry assays showing how stem cell self-renewal modulating proteins, such as PEDF, can statistically significant modify the properties, cell-percentage expressing biomarkers, and carcinogenicity of cancer stem cells (by student t-test). Results: The PEDF signaling pathway could be a useful tool for controlling cancer stem cells’ self-renewal, and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells in vitro culture. We have designed a peptide consisting in the C-terminal part of this protein, which acts by blocking endogenous PEDF in culture cell assays. Conclusion: We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against Docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this PEDF-modified protein produces a significant decrease in the percentage of cancer stem cell expressing markers.

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Pedf derived peptides affect colorectal cancer cell lines resistance and tumour re-growth capacity

Cited by 6 publications

References 48 publications

The m6A Methyltransferase METTL3 Is Functionally Implicated in DLBCL Development by Regulating m6A Modification in PEDF

The m6A Methyltransferase METTL3 Is Functionally Implicated in DLBCL Development by Regulating m6A Modification in PEDF

Moonlighting Role of PEDF in Breast Cancer

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

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