Connective Tissue Growth Factor Immunohistochemical Expression Is Associated With Gallbladder Cancer Progression

García, Patricia; Leal, Pamela; Alvarez, Hector A.; Brebi-Mieville, Priscilla; Ili, Carmen; Tapia, O.; Roa, Juan Carlos

doi:10.5858/arpa.2011-0628-oa

Cited by 10 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study did not show different CTGF expression in GBC and adjacent NT, or the prognostic value of this biomarker. The role of CTGF in GBC progression and its favorable prognostic impact was earlier reported in a Chilean study 28 . This effect may be attributed to the stromal response to the neoplastic process in an autocrine or paracrine manner 28 .…”

Section: Discussionsupporting

confidence: 54%

“…The role of CTGF in GBC progression and its favorable prognostic impact was earlier reported in a Chilean study 28 . This effect may be attributed to the stromal response to the neoplastic process in an autocrine or paracrine manner 28 . Inconsistent results of both studies may be due to different etiology of GBC in the Latin American and Caucasian populations 3,4,6 .…”

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

Hryciuk

Pęksa

Bieńkowski

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Gallbladder cancer (GBc) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (eRα, eRβ, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (nt), and determined their prognostic impact. immunohistochemical (iHc) expression of all biomarkers was performed in formalin-fixed, paraffin-embedded specimens in 60 Caucasian GBC patients (51 women and 9 men). ERβ, cytoPR and CTGF expression were found in 89%, 27%, 91% of GBC, and in 63%, 87%, 100% of NT, respectively. No ERα expression was found in GBC and NT. Strong (3+) HER2 expression by iHc or HER2 amplification was seen in five GBC (10.4%). A positive correlation was found between HER2 and CTGF and ERβ expression in GBc and matched nt. in the multivariate analysis, patient age >70 years, tumor size and ERβ expression in GBc was highly predictive for oS (p = 0.003). The correlation between HER2, CTGF and ERβ expression in GBc and nt may indicate the interaction of these pathways in physiological processes and gallbladder pathology. Gallbladder cancer (GBC) is an aggressive malignant tumor originating from epithelial cells of the mucous membrane. The etiology of GBC is poorly understood, and its global prevalence is characterized by considerable regional variations 1-4. The highest incidence is reported in Chile, India, Pakistan, Bolivia, Central Europe, Israel, and in Native Americans and Americans of Mexican origin 1-4. The risk of developing GBC is higher in patients with chronic inflammatory processes caused by gallstones with resulting calcification of the gallbladder wall ("porcelain gallbladder"), and with infections such as Salmonella typhi or Salmonella paratyphi 3-5. GBC is about two to six times more common in women compared to men, and its incidence steadily increases with age 1-5. Estrogens are key signaling molecules that regulate various physiological processes and play a major role in many pathological conditions, such as hormone-dependent cancers. Expression of female sex hormone receptors in GBC has been analyzed in a few studies including mainly Asian populations, and provided inconsistent results 6-14. Several small studies demonstrated overexpression of human epidermal growth factor receptor type 2 (HER2) and HER gene amplifications or mutations 15-27. Connective Tissue Growth Factor (CTGF) was found to be expressed in various stages of the GBC carcinogenesis 28. GBC carries a poor prognosis and most patients succumb to their disease. An insight into phenotypic features of this tumor may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. In the present study we investigated the expression of female sex hormone receptors: estrogen receptor alpha (ERα), ER beta (ERβ) and progesterone (PR), as well as CTGF and HER2 in a relatively large group of Caucasian GBC pat...

show abstract

Section: Discussionsupporting

confidence: 54%

Section: Discussionsupporting

confidence: 54%

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

Hryciuk

Pęksa

Bieńkowski

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In contrast, in gallbladder cancer higher expression of CTGF in tumour cells leads to better patient outcomes. CTGF is overexpressed compared to normal gallbladder tissue and increases with advancing tumour stage and high CTGF expression correlates with a better survival outcome in patients with advanced gallbladder cancer . Functional studies have revealed that CTGF increases proliferation of gallbladder cancer cells in vitro , suggesting the microenvironment may be responsible for host‐protective functions …”

Section: Ctgf Expression and Clinical Outcomementioning

confidence: 99%

Deregulated expression of connective tissue growth factor (CTGF/CCN2)is linked to poor outcome in human cancer

et al. 2014

View full text Add to dashboard Cite

Connective tissue growth factor (CTGF/CCN2) has long been associated with human cancers. The role it plays in these neoplasms is diverse and tumour specific. Recurring patterns in clinical outcome, histological desmoplasia and mechanisms of action have been found. When CTGF is overexpressed compared to low‐expressing normal tissue or is underexpressed compared to high‐expressing normal tissue, the functional outcome favours tumour survival and disease progression. CTGF acts by altering proliferation, drug resistance, angiogenesis, adhesion and migration contributing to metastasis. The pattern of CTGF expression and tumour response helps to clarify the role of this matricellular protein across a multitude of human cancers.

show abstract

“…CTGF is a key component of wound repair and has been implicated in tumorigenesis [62, 63]. PLAU encodes the urokinase-type plasminogen activator (uPA) which leads to proteolytic degradation of the extracellular matrix (ECM) [64, 65].…”

Section: Discussionmentioning

confidence: 99%

Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness

Low

Png

et al. 2016

Oncotarget

View full text Add to dashboard Cite

The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC) is a malignancy characterized by an intimate relationship between neoplastic cells and a non-neoplastic lymphoid component. Tumor-associated macrophages (TAMs) foster tumor progression through production of soluble mediators that support proliferation, angiogenesis, survival and invasion of malignant cells. However, the role of macrophages in the progression of NPC remains poorly understood. This study aims to investigate the functional and phenotypic changes that occur to macrophages in macrophage-NPC cell co-culture systems, and how these changes influence tumor cells. We found that monocytes, including THP-1 cells and primary human monocytes, co-cultured with C666-1 NPC cells upregulate expression of pro-inflammatory cytokines at the early stages, followed by the induction of metastasis-related genes and interferon-stimulated genes at the later stage of coculture, indicating that TAMs are “educated” by NPC cells for cancer progression. Importantly, the induction of these factors from the TAMs was also found to enhance the migratory capabilities of the NPC cells. We have also identified one of these macrophage-derived factor, phospholipase A2 Group 7 (PLA2G7), to be important in regulating tumor cell migration and a novel tumor-promoting factor in NPC. Further studies to characterize the role of PLA2G7 in tumor metastasis may help determine its potential as a therapeutic target in NPC.

show abstract

Connective Tissue Growth Factor Immunohistochemical Expression Is Associated With Gallbladder Cancer Progression

Abstract: Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

Cited by 10 publications

References 33 publications

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

Deregulated expression of connective tissue growth factor (CTGF/CCN2)is linked to poor outcome in human cancer

Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness

Contact Info

Product

Resources

About