title: Overexpression of HER-2 in MDA-MB-435/LCC6 Tumours is Associated with Higher Metabolic Activity and Lower Energy Stress.
abstract: Overexpresssion of HER-2 in the MDA-MB-435/LCC6 (LCC6(HER-2)) tumour model is associated with significantly increased hypoxia and reduced necrosis compared to isogenic control tumours (LCC6(Vector)); this difference was not related to tumour size or changes in vascular architecture. To further evaluate factors responsible for HER-2-associated changes in the tumour microenvironment, small animal magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure tumour tissue perfusion and metabolism, respectively. The imaging data was further corroborated by analysis of molecular markers pertaining to energy homeostasis, and measurements of hypoxia and glucose consumption. The results showed a strong trend towards higher perfusion rates (~58% greater, p = 0.14), and significantly higher glucose uptake in LCC6(HER-2) (~2-fold greater; p = 0.025), relative to control tumours. The expression of proteins related to energy stress (P-AMPK, P-ACC) and glucose transporters (GLUT1) were lower in LCC6(HER-2) tumours (~2- and ~4-fold, respectively). The in vitro analysis showed that LCC6(HER-2) cells become more hypoxic in 1% oxygen and utilise significantly more glucose in normoxia compared to LCC6(Vector)cells (p < 0.005). Amalgamation of all the data points suggests a novel metabolic adaptation driven by HER-2 overexpression where higher oxygen and glucose metabolic rates produce rich energy supply but also a more hypoxic tumour mass.
authors.affiliation: The Department of Experimental Therapeutics, The BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3.
authors.forename: Wieslawa H
authors.initials: WH
authors.lastname: Dragowska
authors.affiliation: The Joint Department of Medical Imaging, University Health Network, 200 Elizabeth St., Toronto, Ont Canada M5G 2C4.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ginj
authors.affiliation: The High Field MRI Centre at UBC, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC Canada V6T 2B5.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
authors.affiliation: The High Field MRI Centre at UBC, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC Canada V6T 2B5.
authors.forename: Andrew
authors.initials: A
authors.lastname: Yung
authors.affiliation: The TRI-University Meson Facility (TRIUMF), 4004 Wesbrook Mall, Vancouver, BC Canada V6T 2A3.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ruth
authors.affiliation: The TRI-University Meson Facility (TRIUMF), 4004 Wesbrook Mall, Vancouver, BC Canada V6T 2A3.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Adam
authors.affiliation: The Faculty of Physics and Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, BC Canada V6T 1Z1.
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.affiliation: The Department of Experimental Therapeutics, The BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3.|The Faculty of Pathology and Laboratory Sciences, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC Canada V6T 2B5.
authors.forename: Marcel B
authors.initials: MB
authors.lastname: Bally
authors.affiliation: The Department of Experimental Therapeutics, The BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3.|The Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC Canada V6T 1Z3.
authors.forename: Donald T T
authors.initials: DT
authors.lastname: Yapp
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D008279:Magnetic Resonance Imaging; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013312:Stress, Physiological
chemical_list: D005947:Glucose; D018719:Erb-b2 Receptor Tyrosine Kinases