An orthotopic floor‐of‐mouth model for locoregional growth and spread of human squamous cell carcinoma

Henson, Bradley S.; Li, F.; Coatney, Derek D.; Carey, Thomas E.; Mitra, Raj S.; Kirkwood, Keith L.; D’Silva, Nisha J.

doi:10.1111/j.1600-0714.2007.00549.x

Cited by 33 publications

(47 citation statements)

References 19 publications

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“…After injection into the masseter muscle of nude mice, BHY cells developed into highly differentiated squamous cell carcinomas which invaded the mandible, indicating that cathepsin L might help to degrade the bone matrix. This orthotopic animal model, in which tumour cells are injected adjacent to the mandible itself, has been used frequently in early studies of bone invasion [30]. However, based on our lab experience, injecting through the masseter muscle can cause discomfort and feeding difficulties for the animals, Fig.…”

Section: Cathepsinsmentioning

confidence: 98%

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Quan

Johnson

Zhou

et al. 2011

Cancer Metastasis Rev

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Bone invasion is a common characteristic of oral squamous cell carcinoma (OSCC), with adverse affects on patient functionality and survival. Recent studies suggest that it is osteoclasts, rather than malignant keratinocytes themselves, which play the major role in facilitating the entry of the tumour into bone, and its progression within bone. Osteoclasts respond to a variety of local signalling pathways, initiated by products of the malignant epithelial cells. In the present review, we firstly introduce the clinical patterns of bone invasion, and then summarise these signalling pathways and their diverse roles in sequential phases of bone invasion. We also review current researches regarding the incidence and mechanisms of distant metastases to bone, and explain briefly the concept of epithelial-mesenchymal transition, which may generate cancer stem cells and initiate the bone invasion. Finally, we discuss more briefly approaches to the diagnosis and management of OSCC patients with bone invasion. With all these studies and some recent discoveries in our own laboratory, an enhanced understanding of bone invasion will be achieved, which should indicate potential molecular targets for future biotherapies.

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Section: Cathepsinsmentioning

confidence: 98%

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Quan

Johnson

Zhou

et al. 2011

Cancer Metastasis Rev

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“…SCC cells were transfected with pcDNA and pcDNA-FLAG-Rap1GAP plasmids and mixed clonal populations with high Rap1GAP expression were selected in the presence of G418 (250 Ag/mL). The SCC cell line was previously identified as UM-SCC-11A (4,23), but recent genotyping confirmed that it is instead a UM-SCC-1 derivative, an independent cell line from UM-SCC-11A. 6 Two independently transfected mixed clonal populations, one pair (c2 and rg2) transfected by electroporation and the other pair (c1 and rg1) transfected by Lipofectamine, were used, as isolation of multiple single clones was unsuccessful after repeated attempts.…”

Section: Methodsmentioning

confidence: 99%

Rap1GAP Promotes Invasion via Induction of Matrix Metalloproteinase 9 Secretion, Which Is Associated with Poor Survival in Low N-Stage Squamous Cell Carcinoma

et al. 2008

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The objective of the current study was to investigate the effects of Rap1GAP on invasion and progression of head and neck squamous cell carcinoma (SCC) and the role of matrix metalloproteinase (MMP) 9 and MMP2 in this process. Rap1GAP functions by switching off Rap1, the Ras-like protein that has been associated with carcinogenesis. Previous findings suggest that Rap1GAP acts as a tumor suppressor protein in SCC by delaying the G 1 -S transition of the cell cycle. However, cells transfected with Rap1GAP exhibit a more invasive phenotype than corresponding vector-transfected control cells. MMP2 and MMP9 are enzymes that mediate SCC invasion via degradation of the extracellular matrix. Using SCC cells transfected with empty vector or Rap1GAP, cell invasion and MMP secretion were determined by Matrigel assays and gelatin zymography, respectively. Rap1GAP upregulated transcription and secretion of MMP2 and MMP9, as assayed by quantitative reverse transcription-PCR and zymography. Furthermore, chemical and RNA interference blockade of MMP2/MMP9 inhibited invasion by Rap1GAP-transfected cells. Immunohistochemical staining of a human oropharyngeal SCC tissue microarray showed that Rap1GAP and MMP9 expression and staining intensity are correlated (P < 0.0001) and that, in early N-stage lesions of SCC, high MMP9 is prognostic of poor disease-specific survival (P < 0.05). Furthermore, Rap1GAP staining is correlated with MMP2 (P < 0.03). MMP2 in combination with N stage has a prognostic effect on time to indication of surgery at primary site. MMP2 intensity is also positively correlated with T stage (P < 0.015). In conclusion, Rap1GAP inhibits tumor growth but induces MMP2-and MMP9-mediated SCC invasion and tumor progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive SCCs. [Cancer Res 2008;68(10):3959-69]

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“…Work with mice includes both human HNSCC xenografts injected into immunocompromised animals, and immunocompetent animals injected with syngeneic cells [47]. Once tumors are established, they are assessed for growth or proliferation with bioluminescence imaging, 3D visualization through micro-computed topography, or excision followed by light microscopy [48, 49]. The more commonly used approaches will be discussed here, as well as some new in vivo assays.…”

Section: In Vivo Assaysmentioning

confidence: 99%

Reviewing and reconsidering invasion assays in head and neck cancer

2014

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Head and neck squamous cell carcinomas (HNSCC) are malignant tumors that arise from the surface epithelium of the oral cavity, oropharynx and larynx, primarily due to exposure to chemical carcinogens or the human papilloma virus. Due to their location, dental practitioners are well-positioned to detect the lesions. Deadlier than lymphoma or melanoma, HNSCC is incompletely understood. For these reasons, dental practitioners and researchers are focused on understanding HNSCC and the processes driving it. One of these critical processes is invasion, the degradation of the basement membrane by HNSCC cells with subsequent movement into the underlying connective tissue, blood vessels or nerves. Cancer cells metastasize to distant sites via the blood vessels, lymphatics and nerves. Metastasis is associated with poor survival. Since invasion is essential for development and metastasis of HNSCC, it is essential to understand the mechanism(s) driving this process. Elucidation of the mechanisms involved will facilitate the development of targeted treatment, thereby accelerating development of precision/ personalized medicine to treat HNSCC. Robust in vitro and in vivo assays are required to investigate the mechanistic basis of invasion. This review will focus on in vitro and in vivo assays used to study invasion in HNSCC, with special emphasis on some of the latest assays to study HNSCC.

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An orthotopic floor‐of‐mouth model for locoregional growth and spread of human squamous cell carcinoma

Cited by 33 publications

References 19 publications

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Rap1GAP Promotes Invasion via Induction of Matrix Metalloproteinase 9 Secretion, Which Is Associated with Poor Survival in Low N-Stage Squamous Cell Carcinoma

Reviewing and reconsidering invasion assays in head and neck cancer

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