SPARC accelerates biliary tract cancer progression through CTGF-mediated tumor–stroma interactions: SPARC as a prognostic marker of survival after neoadjuvant therapy
- 17.06.2023
- Research
Erschienen in:
- Verfasst von
- Hirotoshi Takayama
- Shogo Kobayashi
- Kunihito Gotoh
- Kazuki Sasaki
- Yoshifumi Iwagami
- Daisaku Yamada
- Yoshito Tomimaru
- Hirofumi Akita
- Tadafumi Asaoka
- Takehiro Noda
- Hiroshi Wada
- Hidenori Takahashi
- Masahiro Tanemura
- Yuichiro Doki
- Hidetoshi Eguchi
- Erschienen in
- Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2023
Abstract
Purpose
In 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).
Methods
We 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.
Results
Among 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).
Conclusion
CTGF 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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- Titel
- SPARC accelerates biliary tract cancer progression through CTGF-mediated tumor–stroma interactions: SPARC as a prognostic marker of survival after neoadjuvant therapy
- Verfasst von
-
Hirotoshi Takayama
Shogo Kobayashi
Kunihito Gotoh
Kazuki Sasaki
Yoshifumi Iwagami
Daisaku Yamada
Yoshito Tomimaru
Hirofumi Akita
Tadafumi Asaoka
Takehiro Noda
Hiroshi Wada
Hidenori Takahashi
Masahiro Tanemura
Yuichiro Doki
Hidetoshi Eguchi
- Publikationsdatum
- 17.06.2023
- Verlag
- Springer Berlin Heidelberg
- Erschienen in
-
Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2023
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335 - DOI
- https://doi.org/10.1007/s00432-023-04835-7
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