ArticleStem cell research & therapy2023
Renal cancer secretome induces migration of mesenchymal stromal cells.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.Experimental hematology & oncology · 2025Review
- hTERT and SV40LgT Renal Cell Lines Adjust Their Transcriptional Responses After Copy Number Changes from the Parent Proximal Tubule Cells.International journal of molecular sciences · 2025Article
- Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells.Cell communication and signaling : CCS · 2025Article
- Lymphovascular Tumoral Emboli in Inflammatory Breast Cancer Result from Haptotaxis-Mediated Encircling Lymphangiogenesis.Lymphatics · 2024Article
- Mesenchymal stromal cells as cancer promoters.Oncogene · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdvanced 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.
methodsConditioned 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.
resultsWhen 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.
conclusionsAdvanced 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.
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