Serum Midkine Correlates with Tumor Progression and Imatinib Response in Gastrointestinal Stromal Tumors

Rawnaq, Tamina; Kunkel, Miriam; Bachmann, Kai; Simon, Ronald; Zander, Hilke; Brandl, Stephan; Sauter, Guido; Izbicki, Jakob R.; Kaifi, Jussuf T.

doi:10.1245/s10434-010-1191-0

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…MK is described as a potential prognostic marker in several malignancies (10,(28)(29)(30)(31)(32). The present study confirmed the frequent overexpression of MK in patient-derived PDAC tissue samples.…”

Section: Discussionsupporting

confidence: 88%

“…In addition, our results explained for the first time how MK may trigger cancer cells to become more resistant against cell death and how it promotes cell viability (9). Recently, we and others have shown that the secretion of MK in tumor cells may serve as biomarker for gastrointestinal tumors and glioblastomas (10,11). Therefore, the development of MK inhibitors has been considered as an attractive idea to prevent tumor growth and antiapoptosis in cancer cells (12,13).…”

Section: Introductionmentioning

confidence: 56%

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The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer

Rawnaq

Dietrich

Wolters‐Eisfeld

et al. 2014

Molecular Cancer Research

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Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis among solid tumors and despite increased knowledge of the molecular mechanisms contributing to progression and metastasis, minimal progress has been done in establishing new targeted therapies for this deadly disease. The expression of the multifunctional growth/ differentiation factor midkine (MK) promotes a variety of cellular functions leading to increased angiogenesis, proliferation, migration, and survival. Moreover, MK is intensively discussed as a potential new-therapy target and as biomarker for cancer progression and chemotherapeutic resistance in multiple cancers. Therefore, the present study investigated the molecular role of MK in pancreatic cancer. It was found that MK is elevated in PDAC and differentially expressed in other histologic subtypes of pancreatic cancer, whereas normal pancreatic cells did not express MK, thus making it an attractive candidate for targeted therapies. As a secreted growth/differentiation factor, MK was investigated as a biomarker in clinical serum specimens using ELISA. In addition, knockdown studies of MK revealed a link to proliferation and migration status in vitro. Finally, upstream signaling pathways were analyzed, with TNF-a and EGF being the main inductors of MK expression in PDAC.Implications: This study presents novel MK functions and new upstream signaling effectors that induce its expression to promote PDAC and therefore defines an attractive new therapeutic target in pancreatic cancer.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 56%

The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer

Rawnaq

Dietrich

Wolters‐Eisfeld

et al. 2014

Molecular Cancer Research

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“…Subjects with MK levels between 650 and 1000 pg·mL −1 would be considered for active surveillance, with re-testing in 3-6 months to determine if MK levels were increasing. Fiegel et al, 2008;Ikematsu et al, 2008;Lucas et al, 2009 Glioblastoma ✓ ✓ Mishima et al, 1997;Stylianou et al, 2009 Meninginoma ✓ ✓ Tong et al, 2007 Neurofibromatosis type 1 ✓ ✓ ✓ Mashour et al, 1999; Gastric ✓ ✓ ✓ ✓ Rha et al, 1997;Ikematsu et al, 2003;Obata et al, 2005;Zhao et al, 2012 GI stromal ✓ ✓ Kaifi et al, 2007;Rawnaq et al, 2011 Bladder Brien et al, 1996;Ikematsu et al, 2003;Fiala et al, 2006;Konety, 2006 (Jia et al, 2007;Zhu et al, 2013), and the oesophageal squamous cell carcinoma markers CEA and cytokeratin 19 fragment (CYFRA21-1) (Shimada et al, 2003). However, despite the apparent superiority of MK over these established circulating biomarkers, it is extremely difficult to displace these markers in standard clinical practice.…”

Section: Mk Overexpression In Diseasementioning

confidence: 99%

Measuring midkine: the utility of midkine as a biomarker in cancer and other diseases

Jones¹

2014

British J Pharmacology

101

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Midkine (MK) is a pleiotropic growth factor prominently expressed during embryogenesis but down-regulated to neglible levels in healthy adults. Many published studies have demonstrated striking MK overexpression compared with healthy controls in various pathologies, including ischaemia, inflammation, autoimmunity and, most notably, in many cancers. MK expression is detectable in biopsies of diseased, but not healthy, tissues. Significantly, because it is a soluble cytokine, elevated MK is readily apparent in the blood and other body fluids such as urine and CSF, making MK a relatively convenient, accessible, non-invasive and inexpensive biomarker for population screening and early disease detection. The first diagnostic tests that quantify MK are just now receiving regulatory clearance and entering the clinic. This review examines the current state of knowledge pertaining to MK as a biomarker and highlights promising indications and clinical settings where measuring MK could make a difference to patient treatment. I also raise outstanding questions about reported variants of MK as well as MK's bio-distribution in vivo. Answering these questions in future studies will enhance our understanding of the significance of measured MK levels in both patients and healthy subjects, and may reveal further opportunities for measuring MK to diagnose disease. MK has already proven to be a biomarker that can significantly improve detection, management and treatment of cancer, and there is significant promise for developing further MK-based diagnostics in the future. LINKED ARTICLEThis article is part of a recent themed section on Midkine, published in volume 171 issue 4. To view the other articles in this section visit http://dx

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“…In our another study, we combined a well known microtubule inhibitor drug vinorelbine with antiphysciotic drug lithium chloride and antidepressant drug clomipramine for neuroblastoma treatment in vitro and showed their novel mechanism of action as MDK inhibitor (Bilir et al, 2010). Rawnaq and coworkers showed that IM, a well known tyrosine kinase inhibitor,decreases MDK levels in the serums of patients with GIST (Rawnaq et al, 2010). In concomitant with these result we showed that IM also decreased MDK levels in human GBM cell lines T98G (Erguven et al, 2011).…”

Section: Midkine Inhibitorsmentioning

confidence: 60%

Midkine Signaling in Glioblastoma: A Novel Developmental Drug Target?

Bılır¹,

Ergüven²

2011

Management of CNS Tumors

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Serum Midkine Correlates with Tumor Progression and Imatinib Response in Gastrointestinal Stromal Tumors

Abstract: S-MK concentration is a potential marker for evaluating the progression and prognosis of GIST, especially during imatinib therapy. Further studies could focus on the role of midkine in the tumorigenesis of GIST and responsiveness toward imatinib therapy.

Cited by 18 publications

References 26 publications

The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer

The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer

Measuring midkine: the utility of midkine as a biomarker in cancer and other diseases

Midkine Signaling in Glioblastoma: A Novel Developmental Drug Target?

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