Expression of midkine in the early stage of carcinogenesis in human colorectal cancer

C, Ye; Mei, Qi; Qw, Fan; K, Ito; Akiyama, Seiji; Kasai, Yasushi; Matsuyama, Mutsushi; Muramatsu, Takashi; Kadomatsu, Kenji

doi:10.1038/sj.bjc.6690030

Cited by 81 publications

(70 citation statements)

References 27 publications

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“…MDK shows highly increased expression in a number of malignant tumors (Nakagawara et al, 1995;O'Brien et al, 1996;Mishima et al, 1997;Ye et al, 1999;Ikematsu et al, 2000;Jia et al, 2007;Maeda et al, 2007) and enhances tumor progression by promoting survival, growth, migration and angiogenic activity Takei et al, 2001;Kadomatsu and Muramatsu, 2004;Mirkin et al, 2005;Tong et al, 2007). In human brain tumors, especially MDK is overexpressed during tumor progression, and patients whose tumors express a higher level of MDK have a worse prognosis (Mishima et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Mashima

Sato²,

Sugimoto

et al. 2008

Oncogene

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Extracellular acidosis (low pH) is a tumor microenvironmental stressor that has a critical function in the malignant progression and metastatic dissemination of tumors. To survive under stress conditions, tumor cells must evolve resistance to stress-induced toxicity. AcylCoA synthetase 5 (ACSL5) is a member of the ACS family, which converts fatty acid to acyl-CoA. ACSL5 is frequently overexpressed in malignant glioma, whereas its functional significance is still unknown. Using retrovirusmediated stable gene transfer (gain of function) and small interfering RNA-mediated gene silencing (loss of function), we show here that ACSL5 selectively promotes human glioma cell survival under extracellular acidosis. ACSL5 enhanced cell survival through its ACS catalytic activity. To clarify the genome-wide changes in cell signaling pathways by ACSL5, we performed cDNA microarray analysis and identified an ACSL5-dependent gene expression signature. The analysis revealed that ACSL5 was critical to the expression of tumor-related factors including midkine (MDK), a heparin-binding growth factor frequently overexpressed in cancer. Knockdown of MDK expression significantly attenuated ACSL5-mediated survival under acidic state. These results indicate that ACSL5 is a critical factor for survival of glioma cells under acidic tumor microenvironment, thus providing novel molecular basis for cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Mashima

Sato²,

Sugimoto

et al. 2008

Oncogene

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“…In the last few years, MK was found to be overexpressed in various human malignant tumours. Northern blot experiments revealed MK mRNA expression in gastric cancers (Aridome et al, 1995(Aridome et al, , 1998, colorectal cancers (Aridome et al, 1995(Aridome et al, , 1998Ye et al, 1999), urinary bladder cancer (O'Brien et al, 1996), neuroblastoma (Nakagawara et al, 1995), Wilm's tumour (Tsutsui et al, 1993), and astrocytoma (Mishima et al, 1997). Interestingly, MK mRNA was reported to be extensively expressed in the early stage of colon cancer carcinogenesis (Ye et al, 1999).…”

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confidence: 99%

Clinical significance of midkine expression in pancreatic head carcinoma

et al. 2007

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Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P ¼ 0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P ¼ 0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P ¼ 0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.

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“…Third, MK is involved in carcinogenesis. Its expression is induced as early as at the precancerous stages of human colorectal and prostate carcinomas (Konishi et al, 1999;Ye et al, 1999), increases with the stages of human carcinomas, and is significantly linked to the prognosis (O'Brien et al, 1996;Mishima et al, 1997). MK transforms NIH3T3 cells , enhances fibrinolysis (Kojima et al, 1995), and promotes cell growth (Muramatsu and Muramatsu, 1991;Muramatsu et al, 1993;Takei et al, 2001), cell survival (Qi et al, 2000), cell migration (Takada et al, 1997;Maeda et al, 1999;Horiba et al, 2000;Qi et al, 2001), and angiogenesis (Choudhuri et al, 1997).…”

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confidence: 99%

Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

et al. 2003

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The heparin-binding growth factor midkine (MK) is the product of a retinoic acid-responsive gene, and is implicated in neuronal survival and differentiation, and carcinogenesis. We previously reported that MK mRNA expression is elevated in neuroblastoma specimens at all stages, whereas pleiotrophin, the other member of the MK family, is expressed at high levels in favourable neuroblastomas. As MK is a secretory protein, it can be detected in the blood. Here, we show a significant correlation of the plasma MK level with prognostic factors of neuroblastomas. The plasma MK level was determined in 220 patients with neuroblastomas, and compared with that in children without malignant tumors (n ¼ 17, o500 pg ml À1 ). The plasma MK level became significantly elevated with advancing stages (stage 1: 445 pg ml À1 (median), n ¼ 73; stage 2: 589, n ¼ 39; stage 3: 864, n ¼ 40; stage 4: 1445, n ¼ 56; and stage 4S: 2439, n ¼ 12). More importantly, a higher MK level was strongly correlated with poor prognostic factors: over 1 year of age (P ¼ 0.0299), MYCN amplification (Po0.0001), low TrkA expression (P ¼ 0.0005), nonmass screening, sporadic neuroblastomas (Po0.0001), and diploidy/tetraploidy (P ¼ 0.0007). Thus, these results demonstrate that the plasma MK level is a good marker for evaluating the progression of neuroblastomas. Moreover, considering the ability of antisense MK oligodeoxyribonucleotide to suppress tumour growth of colorectal carcinoma cells in nude mice, as recently reported, the present study suggests that MK is a possible candidate molecular target for therapy for neuroblastomas.

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Expression of midkine in the early stage of carcinogenesis in human colorectal cancer

Cited by 81 publications

References 27 publications

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Clinical significance of midkine expression in pancreatic head carcinoma

Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

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