Somatic evolution of head and neck cancer — Biological robustness and latent vulnerability

Masuda, Mitsuharu; Toh, Satoshi; Wakasaki, Takahiro; Suzui, Masumi; Joe, Andrew K.

doi:10.1016/j.molonc.2012.10.009

Cited by 17 publications

(17 citation statements)

References 151 publications

(216 reference statements)

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“…Head and neck squamous cell carcinoma (HNSCC) 1 is the sixth most common cancer worldwide with high morbidity and mortality. Treatment options are limited; surgery, radiation and conventional chemotherapy are generally associated with considerable impairment to quality of life (1).…”

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confidence: 99%

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Comparative Secretome Analysis of Epithelial and Mesenchymal Subpopulations of Head and Neck Squamous Cell Carcinoma Identifies S100A4 as a Potential Therapeutic Target

Räsänen

Sriswasdi

Valiga

et al. 2013

Molecular & Cellular Proteomics

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Epithelial-mesenchymal transition (EMT) is a key contributor in tumor progression and metastasis. EMT produces cellular heterogeneity within head and neck squamous cell carcinomas (HNSCC) by creating a phenotypically distinct mesenchymal subpopulation that is resistant to conventional therapies. In this study, we systematically characterized differences in the secretomes of E-cadherin high epithelial-like and E-cadherin low mesenchymal-like subpopulations using unbiased and targeted proteomics. A total 1765 proteins showed significant changes with 177 elevated in the epithelial subpopulation and 173 elevated in the mesenchymal cells. Key nodes in affected networks included NF B, Akt, and ERK, and most implicated cellular components involved various aspects of the extracellular matrix. In particular, large changes were observed in multiple collagens with most affected collagens at much higher abundance levels in the mesenchymal subpopulation. These cells also exhibited a secretome profile resembling that of cancer-associated fibroblastic cells (CAF). S100A4, a commonly used marker for cancer-associated fibroblastic cells, was elevated more than 20-fold in the mesenchymal cells and this increase was further verified at the transcriptome level. S100A4 is a known mediator of EMT, leading to metastasis and EMT has been proposed as a potential source of cancer-associated fibroblastic cells in solid tumors. S100A4 knockdown by small interfering RNA led to decreased expression, secretion and activity of matrix metalloproteinase 2, as verified by quantitative PCR, multiple reaction monitoring and zymography analyses, and reduced invasion in collagen-embedded spheroids. Further confirmation in three-dimensional organotypic reconstructs showed less invasion and advanced differentiation in the S100A4 RNA interference samples. Head and neck squamous cell carcinoma (HNSCC) 1 is the sixth most common cancer worldwide with high morbidity and mortality. Treatment options are limited; surgery, radiation and conventional chemotherapy are generally associated with considerable impairment to quality of life (1). Currently cetuximab, the anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is the only FDA-approved molecularly targeted drug for HNSCC. Several clinical trials are underway that target EGFR or other tyrosine kinases, but many have failed to progress beyond Phase II (2). One reason behind the failure of new treatment options for HNSCC is resistance to therapy, which tumor heterogeneity is thought to provide.

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confidence: 99%

“…Treatment options are limited; surgery, radiation and conventional chemotherapy are generally associated with considerable impairment to quality of life (1). Currently cetuximab, the anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is the only FDA-approved molecularly targeted drug for HNSCC.…”

mentioning

confidence: 99%

Comparative Secretome Analysis of Epithelial and Mesenchymal Subpopulations of Head and Neck Squamous Cell Carcinoma Identifies S100A4 as a Potential Therapeutic Target

Räsänen

Sriswasdi

Valiga

et al. 2013

Molecular & Cellular Proteomics

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“…The preliminary results seem promising in relation to an improvement in the rate of chemoradioselection without significant enhancement of short‐term toxicities. In parallel, we are searching for biological approaches that promote chemoradioselection by targeting cancer stem cell‐like cells in the tumors …”

Section: Discussionmentioning

confidence: 99%

“…In parallel, we are searching for biological approaches that promote chemoradioselection by targeting cancer stem cell-like cells in the tumors. 29…”

Section: Discussionmentioning

confidence: 99%

Utility of algorithm-based chemoradioselection in the treatment for advanced hypopharyngeal carcinoma

et al. 2014

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“…For example, cellular evolution as a basis for neoplastic progression and changes in cancer has been documented in molecular detail in breast cancer [47,62,61], pancreatic cancer [13], renal cancer [28], ovarian cancer [48], leukemia [6,70], colorectal cancer [32], and head and neck cancer [42].…”

Section: The Central Process Of Cancer Biology: Somatic Cellular Evolmentioning

confidence: 99%

Using Systems Biology to Understand Cancer as an Evolutionary Process

Pepper¹,

Dunn²,

Fagerstrom³

et al. 2014

Journal of Evolutionary Medicine

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Unsatisfactory progress in cancer medicine and prevention calls for new research approaches. Research can broaden its view of cancer to include not only specific molecular elements, but also the process that explains their origin and dynamics. This process is Darwinian evolution of somatic cells. Applicable modeling techniques are available from process-oriented systems biology. We review relevant concepts and techniques, and their application to four key open questions in cancer prevention research. Helpful concepts are transferable from classical evolutionary biology and ecology, while useful techniques include computational agent-based modeling. The research questions we review include (1) why do benign neoplasms often progress to malignancy? (2) what is the chronological sequence of molecular events in cancer progression? (3) how can we find reliable molecular biomarkers for cancer? and (4) will evolved drug resistance stymie efforts at a long-term cancer chemoprevention? We conclude that molecular analysis can be usefully augmented with process-oriented systems biology to guide empirical research into the most productive directions.

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Somatic evolution of head and neck cancer — Biological robustness and latent vulnerability

Cited by 17 publications

References 151 publications

Comparative Secretome Analysis of Epithelial and Mesenchymal Subpopulations of Head and Neck Squamous Cell Carcinoma Identifies S100A4 as a Potential Therapeutic Target

Comparative Secretome Analysis of Epithelial and Mesenchymal Subpopulations of Head and Neck Squamous Cell Carcinoma Identifies S100A4 as a Potential Therapeutic Target

Utility of algorithm-based chemoradioselection in the treatment for advanced hypopharyngeal carcinoma

Using Systems Biology to Understand Cancer as an Evolutionary Process

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