PMID- 36070413 OWN - NLM STAT- MEDLINE DCOM- 20221003 LR - 20230110 IS - 1099-0844 (Electronic) IS - 0263-6484 (Print) IS - 0263-6484 (Linking) VI - 40 IP - 7 DP - 2022 Oct TI - Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF-beta production. PG - 760-772 LID - 10.1002/cbf.3742 [doi] AB - Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor-beta 1 (TGF-beta1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF-beta1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki-T) and in monolayers (CaSki-M). Compared with those in CaSki-M cells, CD73 expression and Ado generation ability were significantly increased in CaSki-T cells. CaSki-T cells exhibited enrichment in the CSC-like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki-M cells, CaSki-T cells produced a greater amount of TGF-beta1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class-I (MHC-I) molecules, an increase in the expression of multidrug resistance protein-I (MRP-I) and vimentin, and an increase in the protein expression levels of Snail-1 and Twist, which was strongly reversed with TGF-beta1 inhibition. These results suggest that the presence of TGF-beta1-CD73-Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment. CI - (c) 2022 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd. FAU - Garcia-Rocha, Rosario AU - Garcia-Rocha R AUID- ORCID: 0000-0003-1789-4832 AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. AD - Programa de Beca Posdoctoral UNAM DGAPA-PAPIIT, Ciudad de Mexico, Mexico. FAU - Monroy-Garcia, Alberto AU - Monroy-Garcia A AUID- ORCID: 0000-0002-9733-9013 AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. AD - Laboratorio de Inmunologia y Cancer, UIMEO, H Oncologia, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico. FAU - Carrera-Martinez, Monserrat AU - Carrera-Martinez M AD - Laboratorio de Inmunologia y Cancer, UIMEO, H Oncologia, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico. AD - Programa de Posgrado en Ciencias Biologicas, UNAM, Ciudad de Mexico, Mexico. FAU - Hernandez-Montes, Jorge AU - Hernandez-Montes J AUID- ORCID: 0000-0003-0825-928X AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. FAU - Don-Lopez, Christian Azucena AU - Don-Lopez CA AUID- ORCID: 0000-0001-5857-3440 AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. FAU - Weiss-Steider, Benny AU - Weiss-Steider B AUID- ORCID: 0000-0003-4893-530X AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. FAU - Monroy-Mora, Katia Alheli AU - Monroy-Mora KA AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. FAU - Ponce-Chavero, Maria de Los Angeles AU - Ponce-Chavero MLA AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. AD - Programa de Posgrado en Ciencias Biologicas, UNAM, Ciudad de Mexico, Mexico. FAU - Montesinos-Montesinos, Juan Jose AU - Montesinos-Montesinos JJ AUID- ORCID: 0000-0002-1042-3205 AD - Laboratorio de Celulas Troncales Mesenquimales, Unidad de Investigacion Medica en Enfermedades Oncologicas, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico. FAU - Escobar-Sanchez, Maria Luisa AU - Escobar-Sanchez ML AD - Laboratorio de Microscopia Electronica, Departamento de Biologia Celular, Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Ciudad de Mexico, Mexico. FAU - Castillo, Gabriela Molina AU - Castillo GM AUID- ORCID: 0000-0001-5699-8920 AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. AD - Programa de Posgrado en Ciencias Biologicas, UNAM, Ciudad de Mexico, Mexico. FAU - Chacon-Salinas, Rommel AU - Chacon-Salinas R AUID- ORCID: 0000-0002-4500-0253 AD - Unidad de Desarrollo e Investigacion en Bioprocesos (UDIBI), Instituto Politecnico Nacional, Ciudad de Mexico, Mexico. AD - Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, ENCB-IPN, Ciudad de Mexico, Mexico. FAU - Vallejo-Castillo, Luis AU - Vallejo-Castillo L AUID- ORCID: 0000-0002-9532-3472 AD - Unidad de Desarrollo e Investigacion en Bioprocesos (UDIBI), Instituto Politecnico Nacional, Ciudad de Mexico, Mexico. AD - Departamento de Farmacologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav-IPN), Ciudad de Mexico, Mexico. FAU - Perez-Tapia, Sonia Mayra AU - Perez-Tapia SM AUID- ORCID: 0000-0002-2818-8522 AD - Unidad de Desarrollo e Investigacion en Bioprocesos (UDIBI), Instituto Politecnico Nacional, Ciudad de Mexico, Mexico. AD - Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, ENCB-IPN, Ciudad de Mexico, Mexico. AD - Laboratorio Nacional para Servicios Especializados de Investigacioon, Desarrollo e Innovacion (I+D+i) para Farmoquimicos y Biotecnologicos (LANSEIDI-FarBiotec-CONACyT), Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico City, Mexico. FAU - Mora-Garcia, Maria de Lourdes AU - Mora-Garcia ML AUID- ORCID: 0000-0001-7989-0162 AD - Laboratorio de Inmunobiologia, UIDCC-UMIEZ, FES-Zaragoza, UNAM, Ciudad de Mexico, Mexico. LA - eng GR - FIS/IMSS/PROT/PRIO/19/114 (R2018-3602-015)/Instituto Mexicano del Seguro Social (IMSS)/ GR - IN225519/DGAPA-PAPIIT/ PT - Journal Article DEP - 20220907 PL - England TA - Cell Biochem Funct JT - Cell biochemistry and function JID - 8305874 RN - 0 (Integrin alpha6) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Vimentin) RN - 76057-06-2 (Transforming Growth Factors) RN - EC 3.1.3.5 (5'-Nucleotidase) RN - K72T3FS567 (Adenosine) SB - IM EIN - Cell Biochem Funct. 2022 Dec;40(8):960. PMID: 36316587 MH - 5'-Nucleotidase/metabolism MH - Adenosine/metabolism MH - Cell Line, Tumor MH - Female MH - Humans MH - Integrin alpha6 MH - Transforming Growth Factor beta1/metabolism MH - Transforming Growth Factors MH - Tumor Microenvironment MH - *Uterine Cervical Neoplasms/pathology MH - Vimentin PMC - PMC9825969 OTO - NOTNLM OT - CD73 OT - TGF-beta 1 OT - cancer stem-like (CSC-like) cells OT - cervical cancer OT - protumor phenotype OT - tumorspheres COIS- The authors declare no conflict of interest. EDAT- 2022/09/08 06:00 MHDA- 2022/10/04 06:00 PMCR- 2023/01/08 CRDT- 2022/09/07 14:22 PHST- 2022/08/02 00:00 [revised] PHST- 2022/03/24 00:00 [received] PHST- 2022/08/26 00:00 [accepted] PHST- 2022/09/08 06:00 [pubmed] PHST- 2022/10/04 06:00 [medline] PHST- 2022/09/07 14:22 [entrez] PHST- 2023/01/08 00:00 [pmc-release] AID - CBF3742 [pii] AID - 10.1002/cbf.3742 [doi] PST - ppublish SO - Cell Biochem Funct. 2022 Oct;40(7):760-772. doi: 10.1002/cbf.3742. Epub 2022 Sep 7.