ArticleJournal of cancer research and clinical oncology2023
SPARC accelerates biliary tract cancer progression through CTGF-mediated tumor-stroma interactions: SPARC as a prognostic marker of survival after neoadjuvant therapy.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 2 citations in OpenAlex.
- Intratumoral desmoplastic stroma in carcinoma brain metastases harbors stromal cells with a cancer-associated fibroblast (CAF)-like immunophenotype.Virchows Archiv : an international journal of pathology · 2026Article
- Integrative genomics unveils basement membrane-related diagnostic markers and therapeutic targets in esophageal squamous cell carcinoma.Biology direct · 2024Article
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15 authors at 2 institutions in 1 country.
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Abstract
purposeIn biliary tract cancer (BTC), malignancy is strongest at the invasion front. To improve the BTC prognosis, the invasion front should be controlled. We evaluated tumor-stroma crosstalk at the tumor center and at the invasion front of BTC lesions. We investigated the expression of SPARC, a marker of cancer-associated fibroblasts, and determined its ability to predict BTC prognosis after neoadjuvant chemoradiotherapy (NAC-RT).
methodsWe performed immunohistochemistry to evaluate SPARC expression in resected specimens from patients that underwent BTC surgery. We established highly invasive (HI) clones in two BTC cell lines (NOZ, CCLP1), and performed mRNA microarrays to compare gene expression in parental and HI cells.
resultsAmong 92 specimens, stromal SPARC expression was higher at the invasion front than at the lesion center (p = 0.014). Among 50 specimens from patients treated with surgery alone, high stromal SPARC expression at the invasion front was associated with a poor prognosis (recurrence-free survival: p = 0.033; overall survival: p = 0.017). Coculturing fibroblasts with NOZ-HI cells upregulated fibroblast SPARC expression. mRNA microarrays showed that connective tissue growth factor (CTGF) was upregulated in NOZ-HI and CCLP1-HI cells. A CTGF knockdown suppressed cell invasion in NOZ-HI cells. Exogeneous CTGF upregulated SPARC expression in fibroblasts. SPARC expression at the invasion front was significantly lower after NAC-RT, compared to surgery alone (p = 0.003).
conclusionCTGF was associated with tumor-stroma crosstalk in BTC. CTGF activated stromal SPARC expression, which promoted tumor progression, particularly at the invasion front. SPARC expression at the invasion front after NAC-RT may serve as a prognosis predictor.
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