EGFR and β1-integrin targeting differentially affect colorectal carcinoma cell radiosensitivity and invasion

Poschau, Mandy; Dickreuter, Ellen; Singh-Müller, Jenny; Zscheppang, Katja; Eke, Iris; Liersch, Torsten; Cordes, Nils

doi:10.1016/j.radonc.2015.06.005

Cited by 19 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6–8 Colorectal cancer cell lines cultured in similar laminin-rich ECM 3D conditions also exhibited changes in cellular morphology, phenotype, and gene expression and were resistant to treatment with epidermal growth factor receptor (EGFR) inhibitors compared with 2D cells. 5 , 9 These observations provide a potential explanation for the frequent failure of results derived from conventional 2D cell culture systems to predict clinical efficacy. 10 …”

mentioning

confidence: 98%

A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

Gomez-Roman

Stevenson

Gilmour

et al. 2016

NEUONC

109

View full text Add to dashboard Cite

Background.Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug–radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures.Methods.We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available.Results.In 3 patient-derived GBM lines, no difference in radiation sensitivity was observed between 2D and 3D cultures, as measured by clonogenic survival. Three different molecular targeted agents, for which robust clinical data are available were evaluated in 2D and 3D conditions: (i) temozolomide, which improves overall survival and is standard of care for GBM, exhibited statistically significant effects on clonogenic survival in both patient-derived cell lines when evaluated in the 3D model compared with only one cell line in 2D cells; (ii) bevacizumab, which has been shown to increase progression-free survival when added to standard chemoradiation in phase III clinical trials, exhibited marked radiosensitizing activity in our 3D model but had no effect on 2D cells; and (iii) erlotinib, which had no efficacy in clinical trials, displayed no activity in our 3D GBM model, but radiosensitized 2D cells.Conclusions.Our 3D model reliably predicted clinical efficacy, strongly supporting its clinical relevance and potential value in preclinical evaluation of drug–radiation combinations for GBM.

show abstract

mentioning

confidence: 98%

A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

Gomez-Roman

Stevenson

Gilmour

et al. 2016

NEUONC

109

View full text Add to dashboard Cite

show abstract

“…3D colony formation assay was performed as previously described ( 18 , 19 ). For 3D colony formation, the cells were embedded in 0.5 mg/ml lrECM, 1 mg/ml col-I or a 1:1 mixture of both matrices.…”

Section: Methodsmentioning

confidence: 99%

“…Equal cell numbers were seeded in 3D lrECM or col-I for 96 h. The cells were retrieved by treatment with EDTA or collagenase followed by trypsinization and cell counting using a microscope (Axiovert 40 C; Carl Zeiss Inc.) ( 19 ).…”

Section: Methodsmentioning

confidence: 99%

Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells

et al. 2018

Self Cite

View full text Add to dashboard Cite

Driven by genetic and epigenetic alterations, progression, therapy resistance and metastasis are frequent events in colorectal cancer (CRC). Although often speculated, the function of cell-cell contact for radiochemosensitivity, particularly associated with E-cadherin/catenin complex, warrants further clarification. In this study, we investigated the role of the E-cadherin/catenin complex proteins under more physiological three-dimensional (3D) cell culture conditions in a panel of CRC cell lines. In contrast to floating spheroids and growth in the laminin-rich matrix, collagen type 1 induced the formation of two distinct growth phenotypes, i.e., cell groups and single cells, in 5 out of the 8 CRC cell lines. Further characterization of these subpopulations revealed that, intriguingly, cell-cell contact proteins are important for invasion, but negligible for radiochemosensitivity, proliferation and adhesion. Despite the generation of genomic and transcriptomic data, we were unable to elucidate the mechanisms through which α-catenin affects collagen type 1 invasion. In a retrospective analysis of patients with rectal carcinoma, a low α-catenin expression trended with overall survival, as well as locoregional and distant control. Our results suggest that the E-cadherin/catenin complex proteins forming cell-cell contacts are mainly involved in the invasion, rather than the radiochemosensitivity of 3D grown CRC cells. Further studies are warranted in order to provide a better understanding of the molecular mechanisms controlling cell-cell adhesion in the context of radiochemoresistance.

show abstract

“…β1 integrin is also implicated in resistance to anti-EGFR therapies (Huang et al, 2011 ; Morello et al, 2011 ; Eke et al, 2013 ; Kanda et al, 2013 ). By contrast, a recent study showed that β1 integrin and EGFR inhibitions are inefficient for radio- and chemo-sensitization of colorectal carcinoma cell in vitro (Poschau et al, 2015 ). Cooperation between β1 integrin and c-Met regulates tyrosine kinase inhibitor resistance in lung cancer (Ju and Zhou, 2013 ).…”

Section: Integrins and The Evasion Of Growth Suppressors And The Resimentioning

confidence: 95%

β1 Integrins as Therapeutic Targets to Disrupt Hallmarks of Cancer

et al. 2015

View full text Add to dashboard Cite

Integrins belong to a large family of αβ heterodimeric transmembrane proteins first recognized as adhesion molecules that bind to dedicated elements of the extracellular matrix and also to other surrounding cells. As important sensors of the cell microenvironment, they regulate numerous signaling pathways in response to structural variations of the extracellular matrix. Biochemical and biomechanical cues provided by this matrix and transmitted to cells via integrins are critically modified in tumoral settings. Integrins repertoire are subjected to expression level modifications, in tumor cells, and in surrounding cancer-associated cells, implicated in tumor initiation and progression as well. As critical players in numerous cancer hallmarks, defined by Hanahan and Weinberg (2011), integrins represent pertinent therapeutic targets. We will briefly summarize here our current knowledge about integrin implications in those different hallmarks focusing primarily on β1 integrins.

show abstract

EGFR and β1-integrin targeting differentially affect colorectal carcinoma cell radiosensitivity and invasion

Cited by 19 publications

References 33 publications

A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells

β1 Integrins as Therapeutic Targets to Disrupt Hallmarks of Cancer

Contact Info

Product

Resources

About