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Renal cancer secretome induces migration of mesenchymal stromal cells

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dc.abstract.enBackground Advanced renal cell carcinoma (RCC) is therapeutically challenging. RCC progression is facilitated by mesenchymal stem/stromal cells (MSCs) that exert remarkable tumor tropism. The specific mechanisms mediating MSCs’ migration to RCC remain unknown. Here, we aimed to comprehensively analyze RCC secretome to identify MSCs attractants. Methods Conditioned media (CM) were collected from five RCC-derived cell lines (Caki-1, 786-O, A498, KIJ265T and KIJ308T) and non-tumorous control cell line (RPTEC/TERT1) and analyzed using cytokine arrays targeting 274 cytokines in addition to global CM proteomics. MSCs were isolated from bone marrow of patients undergoing standard orthopedic surgeries. RCC CM and the selected recombinant cytokines were used to analyze their influence on MSCs migration and microarray-targeted gene expression. The expression of genes encoding cytokines was evaluated in 100 matched-paired control-RCC tumor samples. Results When compared with normal cells, CM from advanced RCC cell lines (Caki-1 and KIJ265T) were the strongest stimulators of MSCs migration. Targeted analysis of 274 cytokines and global proteomics of RCC CM revealed decreased DPP4 and EGF, as well as increased AREG, FN1 and MMP1, with consistently altered gene expression in RCC cell lines and tumors. AREG and FN1 stimulated, while DPP4 attenuated MSCs migration. RCC CM induced MSCs’ transcriptional reprogramming, stimulating the expression of CD44, PTX3 and RAB27B. RCC cells secreted hyaluronic acid (HA), a CD44 ligand mediating MSCs’ homing to the kidney. AREG emerged as an upregulator of MSCs’ transcription. Conclusions Advanced RCC cells secrete AREG, FN1 and HA to induce MSCs migration, while DPP4 loss prevents its inhibitory effect on MSCs homing. RCC secretome induces MSCs’ transcriptional reprograming to facilitate their migration. The identified components of RCC secretome represent potential therapeutic targets.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorPiekiełko-Witkowska, Agnieszka
dc.contributor.authorPączek, Leszek
dc.contributor.authorKoblowska, Marta
dc.contributor.authorIwanicka-Nowicka, Roksana
dc.contributor.authorKossowska, Helena
dc.contributor.authorBiałas, Alex
dc.contributor.authorRybicka, Beata
dc.contributor.authorHanusek, Karolina
dc.contributor.authorAdamiok-Ostrowska, Anna
dc.contributor.authorBogusławska, Joanna
dc.contributor.authorBurdzińska, Anna
dc.contributor.authorZarychta-Wiśniewska, Weronika
dc.contributor.authorPopławski, Piotr
dc.date.accessioned2024-01-25T19:11:34Z
dc.date.available2024-01-25T19:11:34Z
dc.date.copyright2023-08-10
dc.date.issued2023
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume14
dc.identifier.doi10.1186/S13287-023-03430-4
dc.identifier.issn1757-6512
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/118388
dc.identifier.weblinkhttps://link.springer.com/content/pdf/10.1186/s13287-023-03430-4.pdf
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofStem Cell Research and Therapy
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enMesenchymal stromal cells
dc.subject.enRenal cell cancer
dc.titleRenal cancer secretome induces migration of mesenchymal stromal cells
dc.typeJournalArticle
dspace.entity.typePublication