Head and Neck Tumor Cell Radiation Response Occurs in the Presence of IGF1

Victory, Kerton R.; Burd, Randy; Fribley, Andrew M.; Sittadjody, Sivanandane; Arnett, D.; Klein, Russell D.; Limesand, Kirsten H.

doi:10.1177/0022034510388037

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…We would expect that high levels of serum IGF1 would be also associated with head and neck cancers, however, Brady et al showed that circulating levels of both IGF1 and IGFBP3 protein is decreased in head and neck cancer patients [27]. On the other hand there is an evidence that IGF1 therepy for head and neck cancer undergoing radiation therapy may help with preservation and restoration of silvary gland function after radiation therapeutical approach [28]. Yet, the study of oral cancer cell line showed that there is positive association between autocrine production of IGF2 together with overexpression of IGF1-R and enhanced proliferation of oral cancer cells [29].…”

Section: Discussionmentioning

confidence: 99%

Expression levels of insulin-like growth factors 1 and 2 in head and neck squamous cell carcinoma

Zhi

Lamperska

Golusiński

et al. 2014

Growth Hormone & IGF Research

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Insulin-like growth factors (IGF) 1 and 2 are known as potential mitogens for normal and neoplastic cells. IGF2 is a main fetal growth factor while IGF1 is activated through growth hormone action during postnatal growth and development. However, there is strong evidence that activation of IGF2 by its E2F transcription factor 3 (E2F3) is present in different types of cancer. Also high levels of IGF1 strongly correlate with cancer development due to anti-apoptotic properties and enhancement of cancer cell differentiation, which can be attenuated by IGFBP3. Head and neck cancer is known as one of the six most common human cancers. The main risk factor for head and neck cancer is consumption of tobacco and alcohol as well as viral and bacterial infection by stimulation of chronic local inflammation. There is also a genetic basis for this form of cancer; however, the genetic markers are not yet established. In this study we investigated the levels of the expression of IGF2, IGF1, E2F3 and IGFBP3 in human cancers and healthy tissues surrounding the tumor obtained from each of 41 patients. Our study indicated that there is no alteration of the level of expression of IGF2, E2F3 and IGF1 in Head and neck squamous cell carcinoma (HNSCC) cases studied in selected experimental population, but there was evidence for upregulation of pro-apoptotic IGFBP3 in cancer when comparing to healthy tissue. These important findings indicate that insulin-growth factors are not directly associated with HNSCC showing some variability between patients and location of tumor. However, elevated level of IGFBP3 suggests possible regulatory role of IGF signal by its binding protein in this type of tumors.

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Section: Discussionmentioning

confidence: 99%

Expression levels of insulin-like growth factors 1 and 2 in head and neck squamous cell carcinoma

Zhi

Lamperska

Golusiński

et al. 2014

Growth Hormone & IGF Research

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“…More recent data, however, suggest that SOCS proteins and especially SOCS2 may also modulate IGF1R-mediated signaling [13], [14]. Importantly, preclinical and translational studies show that components of the IGFR-mediated pathway are implicated in SCCHN risk [15], angiogenesis [16], pharmacogenetics [17], [18], chemosensitivity [19], immunotherapy [20] and radiation response [21].…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

et al. 2013

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IntroductionPrognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.Patients and MethodsWe identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).ResultsAmong 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).ConclusionIGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.

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“…Alternatively, our study suggests that the endogenous pool of salivary LRCs may be stimulated with IGF-1 to promote regeneration. However, although post-therapeutic administration of IGF-1 did not affect tumor growth rates in a xenograft model 50 , systemic administration of growth factors, such as IGF-1, raises concern of increasing the risk of developing de novo malignancies 51 , 52 . One way to circumvent this shortcoming is to develop a delivery mechanism, such as nanoparticles, that allows for targeted administration to the salivary glands.…”

Section: Discussionmentioning

confidence: 99%

aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1

Chibly

Wong

Pier

et al. 2018

Sci Rep

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Xerostomia and salivary hypofunction often result as a consequence of radiation therapy for head and neck cancers, which are diagnosed in roughly 60,000 individuals every year in the U.S. Due to the lack of effective treatments for radiation-induced salivary hypofunction, stem cell-based therapies have been suggested to regenerate the irradiated salivary glands. Pharmacologically, restoration of salivary gland function has been accomplished in mice by administering IGF-1 shortly after radiation treatment, but it is not known if salivary stem and progenitor cells play a role. We show that radiation inactivates aPKCζ and promotes nuclear redistribution of Yap in a population of label-retaining cells in the acinar compartment of the parotid gland (PG)– which comprises a heterogeneous pool of salivary progenitors. Administration of IGF-1 post-radiation maintains activation of aPKCζ and partially rescues Yap’s cellular localization in label retaining cells, while restoring salivary function. Finally, IGF-1 fails to restore saliva production in mice lacking aPKCζ, demonstrating the importance of the kinase as a potential therapeutic target.

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Head and Neck Tumor Cell Radiation Response Occurs in the Presence of IGF1

Cited by 10 publications

References 19 publications

Expression levels of insulin-like growth factors 1 and 2 in head and neck squamous cell carcinoma

Expression levels of insulin-like growth factors 1 and 2 in head and neck squamous cell carcinoma

Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1

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