Research Papers:

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

Paloma Honrubia-Gómez, María-Pilar López-Garrido, Carmen Gil-Gas, José Sánchez-Sánchez, Carmen Alvarez-Simon, Jorge Cuenca-Escalona, Ana Ferrer Perez, Enrique Arias, Raul Moreno, Francisco Sánchez-Sánchez _ and Carmen Ramirez-Castillejo

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Oncotarget. 2019; 10:2973-2986. https://doi.org/10.18632/oncotarget.26085

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Paloma Honrubia-Gómez1, María-Pilar López-Garrido2, Carmen Gil-Gas1, José Sánchez-Sánchez3, Carmen Alvarez-Simon1, Jorge Cuenca-Escalona4, Ana Ferrer Perez5, Enrique Arias6, Raul Moreno7, Francisco Sánchez-Sánchez2 and Carmen Ramirez-Castillejo1,4

1Stem Cell Laboratory, Departamento Ciencias Médicas, CRIB, UCLM, Albacete, Spain

2Genética Médica, Departamento de Ciencia y Tecnología Agroforestal y Genética, IDINE, UCLM, Albacete, Spain

3Current address: Unidad de Oncologia, Hospital de Almansa, Albacete, Spain

4Cancer Stem Cell Laboratory, HST Group, Biotechnology and V Biology Department, ETSIAAB, UPM, Madrid, Spain

5Current address: Oncology Division, Hospital Obispo Polanco, Teruel, Spain

6Departamento de Sistemas Informáticos, UCLM, Albacete, Spain

7UCAM, UCLM, Toledo, Spain

Correspondence to:

Francisco Sánchez-Sánchez, email: [email protected]

Carmen Ramirez-Castillejo, email: [email protected]

Keywords: colorectal cancer stem cells; cancer initiating cells; relapse; self-renewal inhibition; PEDF

Abbreviations: IC50: concentration of drug necessary to kill 50% of the cell population; CT: carboxi-terminal part of the PEDF protein; CTE: carboxi-terminal part of the PEDF protein with a change of a serine by a glutamic; PEDF: Pigmented epithelium derived factor

Received: March 19, 2018     Accepted: August 06, 2018     Published: April 26, 2019


Relapse after chemotherapy treatment depends on the cancer initiating cells (CICs). PEDF (Pigmented Epithelium Derived Factor) is an anti-angiogenic, neurotrophic and self-renewal regulator molecule, also involved in CICs biology. Acute and chronic exposition of colon cancer cell lines to CT/CTE PEDF-derived peptides decreased drug-resistance to conventional colorectal cancer treatments, such as oxaliplatin or irinotecan. We confirmed a reduction in the irinotecan and oxaliplatin IC50 doses for all tested tumour cell lines. After xenograft transplantation, CT/CTE treatments also produced a reduction in resistance to conventional chemotherapy treatments as in culture-assays. Metastatic capacity of these treated cell lines was also depleted. The PEDF signaling pathway could be a future therapeutic tool for use as an adjuvant therapy that decreases IC50 dosis, adverse effects and treatment costs. This pathway could also be involved in an increase of the time relapse in patients, decreased tumourigenicity, and decreased capacity to produce metastasis.

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