Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

Mohanta, Simple; Siddappa, Gangotri; Valiyaveedan, Sindhu Govindan; Ramanjanappa, Ravindra Dodda Thimmasandra; Pandian, Ramanan; Khora, Samanta S.; Kuriakose, Moni Abraham; Suresh, Amritha

doi:10.1177/1010428317703656

Cited by 30 publications

(35 citation statements)

References 52 publications

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“…The cells with high cell surface CD147 expression exhibit characteristic CSC properties, i.e., anchorage‐independent growth, spheroid formation, drug resistance, and invasiveness in vitro , as well as higher tumorigenicity in vivo , but cells expressing low levels of cell surface CD147 do not; the former cells express higher levels of hyaluronan and membrane‐bound CD44, drug transporters, and MCT‐4 than the latter (Dai et al, ). Similar CSC‐like properties were found in CD147 + /CD44 + cells isolated from oral squamous cell carcinoma cells (Mohanta et al, ). In addition, a proteomic study showed that CD147 is important for chemoresistance in breast CSCs (Kang et al, ).…”

Section: Cd147‐hyaluronan Axis In Cancer Stem Cellssupporting

confidence: 69%

The CD147‐HYALURONAN Axis in Cancer

Toole

2019

The Anatomical Record

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CD147 (basigin; EMMPRIN), hyaluronan, and hyaluronan receptors (e.g., CD44) are intimately involved in several phenomena that underlie malignancy. A major avenue whereby they influence tumor progression is most likely their role in the characteristics of cancer stem cells (CSCs), subpopulations of tumor cells that exhibit chemoresistance, invasiveness, and potent tumorigenicity. Both CD147 and hyaluronan have been strongly implicated in chemoresistance and invasiveness, and may be drivers of CSC characteristics, since current evidence indicates that both are involved in epithelial-mesenchymal transition, a crucial process in the acquisition of CSC properties. Hyaluronan is a prominent constituent of the tumor microenvironment whose interactions with cell surface receptors influence several signaling pathways that lead to chemoresistance and invasiveness. CD147 is an integral plasma membrane glycoprotein of the Ig superfamily and cofactor in assembly and activity of monocarboxylate transporters (MCTs). CD147 stimulates hyaluronan synthesis and interaction of hyaluronan with its receptors, in particular CD44 and LYVE-1, which in turn result in activation of multiprotein complexes containing members of the membrane-type matrix metalloproteinase, receptor tyrosine kinase, ABC drug transporter, or MCT families within lipid raft domains. Multivalent hyaluronan-receptor interactions are essential for formation or stabilization of these lipid raft complexes and for downstream signaling pathways or transporter activities. We conclude that stimulation of hyaluronan-receptor interactions by CD147 and the consequent activities of these complexes may be critical to the properties of CSCs and their role in malignancy. Anat Rec, 303:1573Rec, 303: -1583Rec, 303: , 2020

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Section: Cd147‐hyaluronan Axis In Cancer Stem Cellssupporting

confidence: 69%

The CD147‐HYALURONAN Axis in Cancer

Toole

2019

The Anatomical Record

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“…6 ). However, mesenchymal differentiation may also lead to loco-regional or distant metastasis; thus, the complete relationship between differentiation and metastasis appears to be complex, as suggested by studies in oral cancer [ 44 ]. Among our differential 5hmC genes, only CDK6 was identified as a clinically actionable target.…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxymethylation highlights the heterogeneity in keratinization and cell junctions in head and neck cancers

Liu¹,

Medeiros²,

Fernandez³

et al. 2020

Clin Epigenet

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Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide, with human papillomavirus (HPV)-related HNSCC rising to concerning levels. Extensive clinical, genetic and epigenetic differences exist between HPV-associated HNSCC and HPV-negative HNSCC, which is often linked to tobacco use. However, 5-hydroxymethylation (5hmC), an oxidative derivative of DNA methylation and its heterogeneity among HNSCC subtypes, has not been studied. Results We characterized genome-wide 5hmC profiles in HNSCC by HPV status and subtype in 18 HPV(+) and 18 HPV(−) well-characterized tumors. Results showed significant genome-wide hyper-5hmC in HPV(−) tumors, with both promoter and enhancer 5hmC able to distinguish meaningful tumor subgroups. We identified specific genes whose differential expression by HPV status is driven by differential hydroxymethylation. CDKN2A (p16), used as a key biomarker for HPV status, exhibited the most extensive hyper-5hmC in HPV(+) tumors, while HPV(−) tumors showed hyper-5hmC in CDH13, TIMP2, MMP2 and other cancer-related genes. Among the previously reported two HPV(+) subtypes, IMU (stronger immune response) and KRT (more keratinization), the IMU subtype revealed hyper-5hmC and up-regulation of genes in cell migration, and hypo-5hmC with down-regulation in keratinization and cell junctions. We experimentally validated our key prediction of higher secreted and intracellular protein levels of the invasion gene MMP2 in HPV(−) oral cavity cell lines. Conclusion Our results implicate 5hmC in driving differences in keratinization, cell junctions and other cancer-related processes among tumor subtypes. We conclude that 5hmC levels are critical for defining tumor characteristics and potentially used to define clinically meaningful cancer patient subgroups.

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“…A working classification along with some of the markers with prognostic significance is listed in Table 3. [117][118][119][120][121][122][123] It is observed that site-wise distribution of OSCC is responsible for intra and inter-tumoural heterogeneity. In this regard, some authors studied buccal mucosa and tongue OSCC for possible heterogeneity in the cell cycle regulatory mechanism by comparing major cell cycle regulatory proteins.…”

Section: Molecular Markersmentioning

confidence: 99%

Clinico-pathological prognosticators in oral squamous cell carcinoma

Majumdar¹,

Patil

Sarode

et al. 2017

Translational Research in Oral Oncology

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Despite diagnostic and therapeutic advancements, mortality and morbidity rates in the patients diagnosed with oral cancer remain static. Hence, an understanding of the factors that predict the progression of oral cancer appears to be useful in deciding on the most appropriate therapy, thereby improving survival. To do so in practice, a critical knowledge of prognostic markers that have high sensitivity is essential. Though recent research has introduced newer molecular markers, challenging the conventional prognostic assessment methods their universal application is yet to be determined. In practice, clinical and histopathological parameters are widely used for the selection of treatment strategies and for the determination of prognosis in oral cancer patients. A literature search yielded a multitude of parameters to be involved in the determination of prognosis of a patient. Based on published evidence, factors of significance were pTNM, tumour volume, depth of invasion, surgical margin status, tumour budding, vascular and perineural invasion, medullary bone invasion, extracapsular spread and the presence of distant metastasis.

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Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

Cited by 30 publications

References 52 publications

The CD147‐HYALURONAN Axis in Cancer

The CD147‐HYALURONAN Axis in Cancer

5-Hydroxymethylation highlights the heterogeneity in keratinization and cell junctions in head and neck cancers

Clinico-pathological prognosticators in oral squamous cell carcinoma

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