Changes in growth factor levels after thermal ablation in a murine model of colorectal liver metastases

Fifis, Theodora; Malcontenti‐Wilson, Caterina; Amijoyo, Jason; Anggono, Beatrice; Muralidharan, Vijayaragavan; Nikfarjam, Mehrdad; Christophi, Christopher

doi:10.1111/j.1477-2574.2010.00278.x

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…In this study we observed significant upregulation of c-Met and EGFR in liver tissues early Further studies are required to assess this hypothesis in our settings. Interestingly, our group has previously shown that the induction of colorectal liver metastases in this mouse model causes upregulation of TGF-and VEGF in the liver parenchyma by day 21, compared with normal liver (liver with no tumours) [54]. These findings further support the hypothesis of a cross-talk between tumour and stromal cells, both within the tumour and the adjacent liver.…”

Section: Liver Regeneration and Tumour Inductionsupporting

confidence: 75%

Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met

Harun

Costa

Christophi

2013

Clin Exp Metastasis

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Hepatic resection is the preferred option for curative treatment of colorectal liver metastasis (CLM). However, this is associated with significant recurrence rates in both hepatic and extrahepatic sites. The upregulation of growth factors required for liver regeneration after resection is thought to stimulate the growth of micrometastases. The current study describes temporal changes in the expression of hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR) and insulin growth factor I receptor (IGF-IR) in an orthotopic mouse model of liver resection and tumour induction. Mice underwent 70% hepatectomy and induction of liver metastases through intrasplenic injection of colorectal cancer cells. Control groups included sham-operated mice and 70% hepatectomy alone. The expression levels of liver and tumour c-Met, EGFR and IGF-IR were quantified by quantitative RT-PCR at different time points. 70% liver resection stimulates tumour growth; increases the expression of c-Met within established tumours and surrounding liver parenchyma; downregulates EGFR expression and increases IGF-IR expression within the liver parenchyma. In conclusion, we demonstrate in our mouse model that major hepatectomy stimulates engraftment and growth of CLM and that this effect is probably due to the upregulation of c-Met as a result of the liver regeneration process. Liver IGF-IR may also contribute to this phenomenon through a paracrine effect on tumour growth. This study provides support for the role of c-Met in the stimulation of tumour growth after resection possibly through the promotion of tumour cell proliferation.

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Section: Liver Regeneration and Tumour Inductionsupporting

confidence: 75%

Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met

Harun

Costa

Christophi

2013

Clin Exp Metastasis

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“…In a previous study, thermal ablation of murine colorectal liver metastases (CRCLM) was shown to induce the upregulation of HSPA1A in residual tumour cells that peaked at 24 h post-treatment (Nikfarjam et al 2005). In the present study, we used archival tissues from a previous investigation (Fifis et al 2011) to determine whether thermal ablation stimulated an EMT in the residual tumour fraction. Immunohistochemical analysis demonstrated that untreated tumours expressed high levels of E-cadherin ( Fig.…”

Section: Thermal Ablation Treatment Induces Emt In Residual Tumour Frmentioning

confidence: 94%

Heat stress induces epithelial plasticity and cell migration independent of heat shock factor 1

Lang

Nguyen

et al. 2012

Cell Stress and Chaperones

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Current cancer therapies including cytotoxic chemotherapy, radiation and hyperthermic therapy induce acute proteotoxic stress in tumour cells. A major challenge to cancer therapeutic efficacy is the recurrence of therapyresistant tumours and how to overcome their emergence. The current study examines the concept that tumour cell exposure to acute proteotoxic stress results in the acquisition of a more advanced and aggressive cancer cell phenotype. Specifically, we determined whether heat stress resulted in an epithelial-to-mesenchymal transition (EMT) and/or the enhancement of cell migration, components of an advanced and therapeutically resistant cancer phenotype. We identified that heat stress enhanced cell migration in both the lung A549, and breast MDA-MB-468 human adenocarcinoma cell lines, with A549 cells also undergoing a partial EMT. Moreover, in an in vivo model of thermally ablated liver metastases of the mouse colorectal MoCR cell line, immunohistological analysis of classical EMT markers demonstrated a shift to a more mesenchymal phenotype in the surviving tumour fraction, further demonstrating that thermal stress can induce epithelial plasticity. To identify a mechanism by which thermal stress modulates epithelial plasticity, we examined whether the major transcriptional regulator of the heat shock response, heat shock factor 1 (HSF1), was a required component. Knockdown of HSF1 in the A549 model did not prevent the associated morphological changes or enhanced migratory profile of heat stressed cells. Therefore, this study provides evidence that heat stress significantly impacts upon cancer cell epithelial plasticity and the migratory phenotype independent of HSF1. These findings further our understanding of novel biological downstream effects of heat stress and their potential independence from the classical heat shock pathway.

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“…For example, epidermal growth factor receptor activation has been linked to early failure of c-Met inhibition in the treatment of lung cancer (41). Other growth factors and cytokines that have been identified as drivers of tumor growth (including hypoxia-inducible factor-1a and interleukin-6) are also upregulated after RF ablation (4,42). Several of these are linked with c-Met activation through shared downstream mediators or direct involvement in the c-Met pathway (43).…”

Section: Experimental Studies: Suppression Of Radiofrequency Ablationmentioning

confidence: 99%

Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

Ahmed¹,

Kumar²,

Moussa³

et al. 2016

Radiology

109

147

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Changes in growth factor levels after thermal ablation in a murine model of colorectal liver metastases

Abstract: Tumour induces upregulation of TGF-β and VEGF in liver parenchyma. Growth factors decreased after TA, but this appears to be the result of the experimental procedure rather than the TA itself. However, TA resulted in increased levels of TGF-β, which may contribute to tumour recurrence.

Cited by 7 publications

References 37 publications

Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met

Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met

Heat stress induces epithelial plasticity and cell migration independent of heat shock factor 1

Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

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