Spatial distribution of cancer stem cells in head and neck squamous cell carcinomas

Hildebrand, Laura de Campos; Carvalho, Ana Luísa Saraiva Homem de; Lauxen, Isabel S.; Nör, Jacques E.; Cerski, Carlos Thadeu Schmidt; Filho, Manoel Sant’Ana

doi:10.1111/jop.12169

Cited by 23 publications

(29 citation statements)

References 47 publications

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“…Another result that suggests the importance of FAK Tyr‐576 immunostaining in AE was its capacity to differentiate between cases classified as disease‐free survival or failure. These results also highlight the role of FAK Tyr‐576 in proliferation, cellular migration, demonstrating the potential to identify altered epithelial cells in clinically healthy mucosa.…”

Section: Discussionmentioning

confidence: 64%

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Focal adhesion kinases in head and neck squamous cell carcinoma

Flores

Dias

Hildebrand

et al. 2018

J Oral Pathology Medicine

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Section: Discussionmentioning

confidence: 64%

“…Patient's demographic information and tumor clinical data were collected in a previous study (HCPA Ethics Committee No. 09‐315) . The outcome of 5 years of follow‐up was classified as failure (local recurrence, regional, or distant metastasis and death due to tumor) and disease‐free survival.…”

Section: Methodsmentioning

confidence: 99%

Focal adhesion kinases in head and neck squamous cell carcinoma

Flores

Dias

Hildebrand

et al. 2018

J Oral Pathology Medicine

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“…25 Heightened ALDH activity in the invasive perimeter of tumors and even the surrounding extratumoral epithelium has also shown a positive association with aggressiveness and tumor size. 26 The ALDH, Side Population, and ZsGreen-cODC are functional markers and have been used as putative CSC markers in cancers across a range of anatomy. A study with HNSCC cell lines by Vlashi et al 27 reports that the ZsGreen-cODC positive cells (CSCs) are a subset of the ALDH 1 cells.…”

Section: Cellular Markers In Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

“…The CSC characteristics of tumor initiation and therapy resistance have been linked to ALDH activity through phosphotidylinositol‐3‐kinase signaling and SOX2 transcription activity, which has been found to be common to both HPV statuses . Heightened ALDH activity in the invasive perimeter of tumors and even the surrounding extratumoral epithelium has also shown a positive association with aggressiveness and tumor size …”

Section: Introductionmentioning

confidence: 99%

Current understanding of cancer stem cells: Review of their radiobiology and role in head and neck cancers

Reid

Wilson

et al. 2017

Head & Neck

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Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose. This is shown to be not just as a result of preferential killing, but also their capacity to alter divisional dynamics and enlist the support of a complicit microenvironment in therapy resistance and proliferation. The CSCs represent the apex of a hierarchy in the heterogeneity of cancer cells and may be seen as the agents of treatment failure, metastasis, and tumor recurrence, the principal cause of mortality in head and neck cancers. Greater than 90% of head and neck cancers are squamous cell carcinomas (HNSCCs), and among these an increasing incidence of the involvement of the human papillomavirus (HPV) is reported. Chemoradiotherapy along with surgical resection are the interventions of choice for control and cure of HNSCC, but given CSCs therapy resistance and proliferative responses to radiation, the identification and understanding of the radiobiology of this subpopulation is critical to their targeted elimination. This article reviews the current evidence on CSC generally and in HNSCC specifically to identify their phenotype, evaluate their responses to radiotherapy, and evaluate the defensive mechanisms used to resist therapeutic control.

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“…Cancer stem cells primarily reside in the invasive tumor front, an area essential for growth, signal transduction, and cell fate determination (Borovski et al 2011;Hildebrand et al 2014). Tumor cells recruit immunosuppressive cells, such as M2 polarized TAMs, by secreting colony-stimulating factor, TGF-β, and vascular EGF, as well as chemokine ligands 2, 3, 4, 5, and 8 (Coffelt et al 2009).…”

Section: Tumor Immune Network and Relationship With Cancer Stem Cellsmentioning

confidence: 99%

Head and Neck Cancer Stem Cells

2015

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Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer. Annually, more than half a million individuals are diagnosed with this devastating disease, with increasing incidence in Europe and Southeast Asia. The diagnosis of HNSCC often occurs in late stages of the disease and is characterized by manifestation of a high-grade primary tumor and/or lymph node metastasis, precluding timely management of this deadly cancer. Recently, HNSCC cancer stem cells have emerged as an important factor for cancer initiation and maintenance of tumor bulk. Like normal stem cells, cancer stem cells can undergo self-renewal and differentiation. This unique trait allows for maintenance of the cancer stem cell pool and facilitates differentiation into heterogeneous neoplastic progeny when necessary. Recent studies have suggested coexistence of different cancer stem cell populations within a tumor mass, where the tumor initiation and metastasis properties of these cancer stem cells can be uncoupled. Cancer stem cells also possess resistant phenotypes that evade standard chemotherapy and radiotherapy, resulting in tumor relapse. Therefore, understanding distinctive pathways relating to cancer stem cells will provide insight into early diagnosis and treatment of HNSCC. In this review, we highlight current advances in identifying cancer stem cells, detail the interactions of these cells with the immune system within the tumor niche, and discuss the potential use of immunotherapy in managing HNSCC.Keywords: flow cytometry, tumor microenvironment, squamous cell carcinoma of the head and neck, neoplastic stem cells, tumor immunology, metastasis

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Spatial distribution of cancer stem cells in head and neck squamous cell carcinomas

Cited by 23 publications

References 47 publications

Focal adhesion kinases in head and neck squamous cell carcinoma

Focal adhesion kinases in head and neck squamous cell carcinoma

Current understanding of cancer stem cells: Review of their radiobiology and role in head and neck cancers

Head and Neck Cancer Stem Cells

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