Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant Lung Cancer Cells

Sun, Yunguang; Zheng, Siyuan; Torossian, Artour; Speirs, Christina K.; Schleicher, Stephen M.; Giacalone, Nicholas J.; Carbone, David P.; Zhao, Zhongming; Lü, Bo

doi:10.1016/j.ijrobp.2011.06.1999

Cited by 63 publications

(55 citation statements)

References 20 publications

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“…Bitelman et al [46] reported that cisplatin-resistant cells demonstrating increased activation of the IGF1 pathway recovered their sensitivity to cisplatin after small interfering RNA treatment. IGF1R activation has been known to protect tumor cells against apoptosis induced by cytotoxic drugs, and may also influence the repair of DNA damage [47]. From our research and the other results cited here, it is clear that activation of the IGF1 pathway is relevant to the maintenance of stemness.…”

Section: Discussionsupporting

confidence: 72%

Maintenance of Stemness in Oxaliplatin-Resistant Hepatocellular Carcinoma Is Associated with Increased Autocrine of IGF1

et al. 2014

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BackgroundEvidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generating CSCs. In the present study, we investigate whether oxaliplatin-treated cancer tissues possess characteristics of CSCs, and explore oxaliplatin resistance in these tissues.MethodsHepatocellular carcinoma cells (MHCC97H cells) were subcutaneously injected into mice to form tumors, and the mice were intravenously treated with either oxaliplatin or glucose. Five weeks later, the tumors were orthotopically xenografted into livers of other mice, and these mice were treated with either oxaliplatin or glucose. Metastatic potential, sensitivity to oxaliplatin, and expression of CSC-related markers in the xenografted tumor tissues were evaluated. DNA microarrays were used to measure changes in gene expression as a result of oxaliplatin treatment. Additionally, an oxaliplatin-resistant cell line (MHCC97H-OXA) was established to assess insulin-like growth factor 1 secretion, cell invasion, cell colony formation, oxaliplatin sensitivity, and expression of CSC-related markers. The effects of an insulin-like growth factor 1 receptor inhibitor were also assessed.ResultsOxaliplatin treatment inhibited subcutaneous tumor growth. Tumors from oxaliplatin-treated mice that were subsequently xenografted into livers of other mice exhibited that decreasing sensitivity to oxaliplatin and increasing pulmonary metastatic potential. Among the expression of CSC-related proteins, the gene for insulin-like growth factor 1, was up-regulated expecially in these tumor tissues. Additionally, MHCC97H-OXA cells demonstrated that increasing cell invasion, colony formation, and expression of insulin-like growth factor 1 and CSC-related markers, whereas treatment with an inhibitor of the insulin-like growth factor 1 receptor suppressed these effects.ConclusionMaintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1.

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Section: Discussionsupporting

confidence: 72%

Maintenance of Stemness in Oxaliplatin-Resistant Hepatocellular Carcinoma Is Associated with Increased Autocrine of IGF1

et al. 2014

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“…Increased IGF-1 receptor expression in NSCLC is associated with poor prognosis [93], and IGF-1 receptor expression was noted to be higher in hepatocellular carcinoma cancer stem cells [94]. Cisplatin resistant lung cancer cells were found to have increased IGF-1 receptor signaling [95]. …”

Section: Laboratory Evidence and The Basis For Further Clinical Trialsmentioning

confidence: 99%

The Links Between Insulin Resistance, Diabetes, and Cancer

2012

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The growing epidemic of obesity has resulted in a large increase in multiple related diseases. Recent evidence has strengthened the proposed synergistic relationship between obesity-related insulin resistance (IR) and/or diabetes mellitus (DM) and cancer. Within the past year, many studies have examined this relationship. Although the precise mechanisms and pathways are uncertain, it is becoming clear that hyperinsulinemia and possibly sustained hyperglycemia are important regulators of not only the development of cancer but also of treatment outcome. Further, clinical decision-making regarding the treatment of choice for DM will likely be impacted as we learn more about the non-metabolic effects of the available hyperglycemic agents. In our review, we endeavored to synthesize the recent literature and provide a concise view of the journey from macro-level clinical associations to specific mechanistic relationships being elucidated in cell lines and animal models.

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“…However, Yamamoto et al (2012) claimed that IGF1R overexpression was related to lymph node metastasis and tumor recurrence. Also, Sun et al (2012) claimed that IGF1R expression played a role in the development of resistance to cisplatin and radiotherapy in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Lack of any Prognostic Role of Insulin-Like Growth Factor-1 Receptor in Non-Small Cell Lung Cancer

Dilli¹,

Yıldırım²,

Süren³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: The purpose of this study is to determine whether the IGF1R expression has a prognostic role in non-small cell lung cancer. Materials and Methods: Forty-seven patients histopathologically diagnosed with small cell lung cancer upon bronchoscopic biopsy or resection materials were included in the study. IGF1R expression was examined via immunohistochemical methods. In samples, >10% staining were assessed as positive and ≤10% as negative. Information about demographic datas and treatments was obtained by retrospective searches of patient files. Results: IGF1R expression was determined as positive in 38 (80.9%) and as negative in 9 (19.1%) patients. There was no significant relation between IGF1R expression and histological sub-type, local invasion, lymph node and metastasis status (p=0.842, p=0.437, 0.064, 0.447, respectively). There was also no correlation with IGF1R expression and survival (p=0.141). Conclusions: There are conflicting results between IGF1R and its prognostic effects in the various studies. It has been claimed in some studies it is not related to prognosis as in our study, and in some studies it has been claimed that it is a good prognostic factor whereas in some studies it has been claimed as being a factor for worse prognosis. We think that IGF1R expression in non-small cell lung carcinoma patients deserves further analysis, because of its potential prognostic and predictive roles.

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Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant Lung Cancer Cells

Cited by 63 publications

References 20 publications

Maintenance of Stemness in Oxaliplatin-Resistant Hepatocellular Carcinoma Is Associated with Increased Autocrine of IGF1

Maintenance of Stemness in Oxaliplatin-Resistant Hepatocellular Carcinoma Is Associated with Increased Autocrine of IGF1

The Links Between Insulin Resistance, Diabetes, and Cancer

Lack of any Prognostic Role of Insulin-Like Growth Factor-1 Receptor in Non-Small Cell Lung Cancer

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