Suppressive effect of overexpressed connective tissue growth factor on tumor cell growth in a human oral squamous cell carcinoma-derived cell line

Moritani, Norifumi; Kubota, Satoshi; Nishida, Takashi; Kawaki, Harumi; Kondo, Seiji; Sugahara, Toshio; Takigawa, Masaharu

doi:10.1016/s0304-3835(02)00718-8

Cited by 54 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although CTGF was found to be overexpressed in oesophageal carcinoma (Koliopanos et al 2002), highest levels were associated with longer survival in squamous cell carcinoma, but with shorter survival in adenocarcinoma. In squamous cell carcinoma of the oesophagus, high levels of CTGF are associated with longer survival (Koliopanos et al 2002), and overexpression of CTGF in oral squamous cell carcinoma is associated with slower growth (Moritani et al 2003). In breast cancer, CTGF has been found to be associated with nodal status and tumour size (Xie et al 2001a).…”

Section: Discussionmentioning

confidence: 99%

“…Transfection of MCF-7 with CTGF expression vector results in a high degree of apoptosis (Hishikawa et al 1999). This has been supported partly by a recent study which shows that over-expression of CTGF in oral squamous cell carcinoma results in reduction in cell growth and tumorigenesis (Moritani et al 2003). Nov/CCN3 is probably the least-studied CCN member.…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer

Jiang¹,

Watkins²,

Fodstad³

et al. 2004

Endocr Relat Cancer

159

134

View full text Add to dashboard Cite

The CCN family members cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/ CCN2) and nephroblastoma over-expressed (Nov/CCN3) play diverse roles in cells, are known to regulate cell growth, adhesion, matrix production and migration and are involved in endocrineregulated pathways in various cell types. The role of these molecules in cancer remains controversial. In a cohort of 122 human breast tumours (together with 32 normal breast tissues) we have analysed the expression of all three CCN members at the mRNA and protein levels. Significantly higher levels of Cyr61 ðP ¼ 0:02Þ, but low levels of CTGF and Nov, were seen in tumour tissues compared with normal tissues. Significantly raised levels of Cyr61 were associated with poor prognosis ðP ¼ 0:02Þ, nodal involvement ðP ¼ 0:03Þ and metastatic disease ðP ¼ 0:016Þ. Patients who died of breast cancer also had high levels of Cyr61. In contrast, CTGF in patients with poor prognosis ðP ¼ 0:021Þ, metastasis ðP ¼ 0:012Þ, local recurrence ðP ¼ 0:0024Þ and mortality ðP ¼ 0:0072Þ had markedly reduced levels. Similar to CTGF, low levels of Nov were also seen in patients with poor prognosis and mortality and with significantly decreased survival (P ¼ 0:033 and P ¼ 0:0146, respectively). This result was fully supported by immunohistochemical analysis of frozen sectioned tissues. While fibroblasts and endothelial cells generally expressed good levels of all three CCN proteins, highly invasive MDA MB 231 cells expressed lower levels of CTGF and Nov, but higher levels of Cyr61, than the less invasive MCF-7. It is concluded that members of the CCN family are differentially expressed and may play important but contrasting roles in the progressive nature of human breast cancer. While Cyr61 appears to act as a factor stimulating aggressiveness, CTGF and Nov may act as tumour suppressors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer

Jiang¹,

Watkins²,

Fodstad³

et al. 2004

Endocr Relat Cancer

159

134

View full text Add to dashboard Cite

show abstract

“…26,27 In contrast, several other studies have reported a relation between the overexpression of CTGF and cancer inhibition. 28,29 Interestingly, CTGF induces apoptosis in MCF-7 cells and aortic smooth muscle cells. 30,31 A recent study suggested that loss of CRYAB expression might be involved in promoting ovarian tumorigenesis or tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Id-1gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer

2005

View full text Add to dashboard Cite

The molecular mechanisms underlying the chemopreventive effects of NSAIDs are not well understood and remain the subject of debate. One of the mechanistic possibilities involves alterations in gene expression. We examined gene expression profiles in SNU601 gastric cancer cells treated with sulindac sulfide (50 lM) for 24 hr. Microarray analysis showed that 1.3% (105/8170) of genes were induced or repressed more than 3-fold in cells treated with sulindac sulfide. Seven genes were selected and confirmed by reverse transcription-polymerase chain reaction. Inhibitor of differentiation/DNA binding-1 (Id-1) was downregulated in SNU601 cells treated with sulindac sulfide. Id-1 expression level was decreased dose-dependently by sulindac sulfide. In addition, the expression pattern of Id-1 was inversely related to that of nm23. We also examined Id-1 expression in human gastric cancer tissues and compared it with clinicopathologic parameters to study its biologic role in the cancers. Id-1 was frequently and strongly expressed in gastric cancer tissues compared with that in adjacent nonmetaplastic mucosa. Its immunoreactivity scores were positively correlated to Ki67 labeling indices and tumor progression, and is higher in intestinal type than in diffuse type. In summary, a number of genes, both induced and repressed, could be important in mediating sulindac sulfide-induced cell death in gastric cancer cells. Id-1, one of the repressed genes, is upregulated in gastric cancers and has positive role in tumor progression and histogenesis of intestinal-type cancers. ' 2005 Wiley-Liss, Inc.

show abstract

“…Elevated CTGF levels have been detected in a number of cancers including pancreatic (15), breast (16), glioblastoma (17,18), esophageal (19), melanoma (20), chondrosarcoma (21), oral squamous cell cancer (22), acute lymphoblastic leukemia (23), rhabdomyosarcoma (24), and hepatocellular carcinoma (25), but its direct role in tumor suppression or progression has not been investigated in pancreatic cancer nor with therapeutic agents with the capacity to inhibit CTGF function in vivo. An increase in CTGF was reported to be associated with decreased survival of patients with breast cancer (16), glioblastoma (18), or adenocarcinoma of the esophagus (19), and increased breast cancer bone metastasis in a mouse model (26).…”

Section: Introductionmentioning

confidence: 99%

Connective Tissue Growth Factor–Specific Monoclonal Antibody Therapy Inhibits Pancreatic Tumor Growth and Metastasis

et al. 2006

View full text Add to dashboard Cite

Pancreatic cancer is highly aggressive and refractory to most existing therapies. Past studies have shown that connective tissue growth factor (CTGF) expression is elevated in human pancreatic adenocarcinomas and some pancreatic cancer cell lines. To address whether and how CTGF influences tumor growth, we generated pancreatic tumor cell lines that overexpress different levels of human CTGF. The effect of CTGF overexpression on cell proliferation was measured in vitro in monolayer culture, suspension culture, or soft agar, and in vivo in tumor xenografts. Although there was no effect of CTGF expression on proliferation in two-dimensional cultures, anchorage-independent growth (AIG) was enhanced. The capacity of CTGF to enhance AIG in vitro was linked to enhanced pancreatic tumor growth in vivo when these cells were implanted s.c. in nude mice. Administration of a neutralizing CTGF-specific monoclonal antibody, FG-3019, had no effect on monolayer cell proliferation, but blocked AIG in soft agar. Consistent with this observation, anti-CTGF treatment of mice bearing established CTGF-expressing tumors abrogated CTGF-dependent tumor growth and inhibited lymph node metastases without any toxicity observed in normal tissue. Together, these studies implicate CTGF as a new target in pancreatic cancer and suggest that inhibition of CTGF with a human monoclonal antibody may control primary and metastatic tumor growth. (Cancer Res 2006; 66(11): 5816-27)

show abstract

Suppressive effect of overexpressed connective tissue growth factor on tumor cell growth in a human oral squamous cell carcinoma-derived cell line

Cited by 54 publications

References 28 publications

Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer

Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer

Id-1gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer

Connective Tissue Growth Factor–Specific Monoclonal Antibody Therapy Inhibits Pancreatic Tumor Growth and Metastasis

Contact Info

Product

Resources

About