Colorectal cancer cells induce the formation of cancer-associated fibroblasts by activating the ERK signaling pathway in fibroblasts
OBJECTIVE: To investigate the mechanism by which conditioned medium of colorectal cancer cells promotes the formation of cancer-associated fibroblasts (CAFs).
METHODS: Normal human colorectal fibroblasts (CCD-18Co cells) in logarithmic growth phase were treated with the conditioned media of colorectal cancer HCT116 cells (HCT116-CM) or Caco-2 cells (Caco-2-CM) alone or in combination with 300 nmol/L ERK inhibitor SCH772984. The expression levels of CAFs-related molecular markers were detected in the treated cells with real-time quantitative PCR (RT- qPCR) and immunofluorescence assay, and the changes in cell proliferation, colony formation and migration were assessed with RTCA, colony formation and wound healing assays; Western blotting was performed to detect the activated signaling pathways in the fibroblasts and the changes in CAFs formation after blocking of the signaling pathway.
RESULTS: HCT116-CM and Caco-2-CM significantly upregulated mRNA expression levels of CAFs markers (including α-SMA, FAP, FN and TGF-β) in CCD-18Co cells, and strongly promoted fibroblast transformation into CAFs (P < 0.05). The two conditioned media also promoted the proliferation, colony formation and migration of CCD-18Co cells (P < 0.05) and significantly increased the levels of α-SMA protein and ERK phosphorylation in the cells (P < 0.05). The ERK inhibitor SCH772984 obviously inhibited the expression of α-SMA and the transformation of CCD-18Co cells into CAFs induced by the conditioned medium of colorectal cancer cells (P < 0.05).
CONCLUSION: Colorectal cancer cells may induce the formation of colorectal CAFs by activating the ERK pathway in the fibroblasts.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Nan fang yi ke da xue xue bao = Journal of Southern Medical University - 43(2023), 6 vom: 20. Juni, Seite 943-951 |
| Sprache: |
Chinesisch |
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| Beteiligte Personen: |
Deng, T [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer-associated fibroblasts |
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| Anmerkungen: |
Date Completed 14.07.2023 Date Revised 18.07.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.12122/j.issn.1673-4254.2023.06.09 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359399665 |
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| 245 | 1 | 0 | |a Colorectal cancer cells induce the formation of cancer-associated fibroblasts by activating the ERK signaling pathway in fibroblasts |
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| 500 | |a Date Completed 14.07.2023 | ||
| 500 | |a Date Revised 18.07.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To investigate the mechanism by which conditioned medium of colorectal cancer cells promotes the formation of cancer-associated fibroblasts (CAFs) | ||
| 520 | |a METHODS: Normal human colorectal fibroblasts (CCD-18Co cells) in logarithmic growth phase were treated with the conditioned media of colorectal cancer HCT116 cells (HCT116-CM) or Caco-2 cells (Caco-2-CM) alone or in combination with 300 nmol/L ERK inhibitor SCH772984. The expression levels of CAFs-related molecular markers were detected in the treated cells with real-time quantitative PCR (RT- qPCR) and immunofluorescence assay, and the changes in cell proliferation, colony formation and migration were assessed with RTCA, colony formation and wound healing assays; Western blotting was performed to detect the activated signaling pathways in the fibroblasts and the changes in CAFs formation after blocking of the signaling pathway | ||
| 520 | |a RESULTS: HCT116-CM and Caco-2-CM significantly upregulated mRNA expression levels of CAFs markers (including α-SMA, FAP, FN and TGF-β) in CCD-18Co cells, and strongly promoted fibroblast transformation into CAFs (P < 0.05). The two conditioned media also promoted the proliferation, colony formation and migration of CCD-18Co cells (P < 0.05) and significantly increased the levels of α-SMA protein and ERK phosphorylation in the cells (P < 0.05). The ERK inhibitor SCH772984 obviously inhibited the expression of α-SMA and the transformation of CCD-18Co cells into CAFs induced by the conditioned medium of colorectal cancer cells (P < 0.05) | ||
| 520 | |a CONCLUSION: Colorectal cancer cells may induce the formation of colorectal CAFs by activating the ERK pathway in the fibroblasts | ||
| 650 | 4 | |a English Abstract | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ERK singaling | |
| 650 | 4 | |a cancer-associated fibroblasts | |
| 650 | 4 | |a colorectal cancer | |
| 650 | 4 | |a tumor microenvironment | |
| 650 | 7 | |a Culture Media, Conditioned |2 NLM | |
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| 700 | 1 | |a Xi, X |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:43 |g year:2023 |g number:6 |g day:20 |g month:06 |g pages:943-951 |
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