---
title: "CTGF/CCN2 Drives Invasive Growth in Cervical Cancer and Associates With Metastasis"
id: "pubmed-42674826"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42674826"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42674826/"
doi: "10.21873/cgp.20609"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CTGF/CCN2 Drives Invasive Growth in Cervical Cancer and Associates With Metastasis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42674826
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42674826/)
- **DOI:** [10.21873/cgp.20609](https://doi.org/10.21873%2Fcgp.20609)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study examines the role of **CTGF/CCN2** (connective tissue growth factor) in promoting invasive behavior of cervical cancer (CC) using 3D spheroid models and patient tissue samples. - Two cervical cancer cell lines (C33A, HT3) grown as spheroids were exposed to recombinant human CTGF (rhCTGF) or a CTGF-blocking antibody (IgG CTGF) and assessed in a 3D invasion assay. - Functional blockade of CTGF produced a statistically significant reduction in 3D spheroid invasive growth for both C33A and HT3 cells (p < 0.0001). - Immunofluorescence in spheroids showed that rhCTGF induced surface clustering of the stemness marker **CD133** and peripheral enrichment of **N-cadherin**, while CTGF blockade correlated with nuclear/perinuclear enrichment of CD133 and **E-cadherin**, and reduced N-cadherin signal. - A tissue microarray of 69 cervical lesion cases (pre-invasive, invasive FIGO I–III, and metastatic lesions), sampled in triplicate, was used to quantify CTGF expression by immunofluorescence scoring. - Metastatic tissue cores displayed the highest CTGF fluorescence intensity among the categories examined. - High CTGF expression (immunoreactivity score ≥ 6) was most common in FIGO stage I lesions (35.5%) and less common in FIGO stage III (10.0%). - Kaplan-Meier analysis reported that elevated CTGF mRNA expression correlated with significantly reduced recurrence-free survival (log-rank p = 0.0032). - Authors conclude CTGF appears to regulate an invasive phenotype in 3D CC models, likely via altered localization of stemness and EMT markers, and suggest CTGF may act as an early prognostic biomarker linked to metastatic potential. - Details such as exact sample composition by histology, complete quantitative metrics for tissue scoring beyond percentages reported, and mechanistic pathways beyond marker localization were not reported in the abstract.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany. * 2 Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany grundker@med.uni-goettingen.de. * PMID: **42674826** * DOI: [ 10.21873/cgp.20609 ](https://doi.org/10.21873/cgp.20609) Item in Clipboard # CTGF/CCN2 Promotes Invasive Growth in Cervical Cancer Spheroids and Is Associated With Metastatic Cervical Cancer Tissue Linda VON DER Brelie et al. Cancer Genomics Proteomics. 2026 Sep-Oct. Show details Display options Display options Format Abstract PubMed PMID Cancer Genomics Proteomics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Genomics+Proteomics%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Genomics+Proteomics%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42674826/) . 2026 Sep-Oct;23(5):934-947. doi: 10.21873/cgp.20609. ### Authors [Linda VON DER Brelie](https://pubmed.ncbi.nlm.nih.gov/?term=VON+DER+Brelie+L&cauthor_id=42674826)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674826/#short-view-affiliation-1 "Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany."), [Nesibe Gökçe Kalyoncu](https://pubmed.ncbi.nlm.nih.gov/?term=Kalyoncu+NG&cauthor_id=42674826)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674826/#short-view-affiliation-1 "Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany."), [Julia Gallwas](https://pubmed.ncbi.nlm.nih.gov/?term=Gallwas+J&cauthor_id=42674826)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674826/#short-view-affiliation-1 "Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany."), [Carsten Gründker](https://pubmed.ncbi.nlm.nih.gov/?term=Gr%C3%BCndker+C&cauthor_id=42674826)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674826/#short-view-affiliation-2 "Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany grundker@med.uni-goettingen.de.") ### Affiliations * 1 Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany. * 2 Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany grundker@med.uni-goettingen.de. * PMID: **42674826** * DOI: [ 10.21873/cgp.20609 ](https://doi.org/10.21873/cgp.20609) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background/aim:** Metastatic spread defines the lethality of cervical cancer (CC). Connective tissue growth factor (CTGF/CCN2) regulates cell- extracellular matrix interactions but its role in CC is not well-defined. This study investigates the role of CTGF in driving CC invasive growth and its prevalence in patient tissues. **Materials and methods:** CC spheroids (C33A, HT3) were treated with recombinant human CTGF (rhCTGF) or a function-blocking antibody (IgG CTGF). Invasive growth was assessed via 3D spheroid assay using a Celigo imaging cytometer. Cancer stem cell (CD133, CD44) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin) were analyzed by immunofluorescence. CTGF expression was evaluated using a tissue microarray containing 69 cases in triplicate from pre-invasive, invasive (FIGO I-III), and metastatic cervical lesions, quantified via immunofluorescence scoring. **Results:** Functional blockade of CTGF significantly reduced 3D spheroid invasive growth in C33A and HT3 cells (_p_ <0.0001). Immunofluorescence revealed that CTGF modulation altered spatial distribution of key proteins: rhCTGF induced surface clustering of CD133 and peripheral N-cadherin enrichment, while CTGF blockade was associated with apparent nuclear/perinuclear enrichment of CD133 and E-cadherin and reduced N-cadherin signal. In patient tissue cores, metastatic samples exhibited the highest CTGF fluorescence intensity. High CTGF expression [immunoreactivity score (IRS) ≥ 6] was most prevalent in FIGO stage I (35.5%) compared to stage III (10.0%). Kaplan-Meier analysis revealed that high CTGF mRNA expression was associated with significantly reduced recurrence-free survival (log-rank _p_ =0.0032). **Conclusion:** In 3D models of CC, CTGF appears to regulate an invasive phenotype, presumably by controlling aberrant localization of stemness and EMT markers. Its apparently elevated expression in early-stage cervical carcinomas and metastases, combined with its prognostic value for recurrence-free survival, suggests that CTGF may be involved in triggering the potential for metastasis and could therefore serve as an early prognostic biomarker. **Keywords:** CC; CCN2; CTGF; Connective tissue growth factor; cervical cancer; invasion; metastasis. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. 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