Key proteins of invadopodia are overexpressed in oral squamous cell carcinoma suggesting an important role of MT1-MMP in the tumoral progression

Diagn Pathol. 2021 Apr 20;16(1):33. doi: 10.1186/s13000-021-01090-7.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is the most relevant malignant neoplasm among all head and neck tumours due to its high prevalence and unfavourable prognosis. Tumour invasion and metastasis that affect prognosis are result of a set of complex events that cells with invasive potential use to spread to other regions. These cells use several mechanisms to invade tissues, including a type of finger-like membrane protrusion called invadopodia. This study aims to investigate the immunoexpression of invaopodia related-proteins TKs5, cortactin, TKs4 and MT1-MMP in OSCC and correlate it to clinicopathological data.

Methods: An immunohistochemical evaluation of fifty cases of OSCCs and 20 cases of oral mucosa (OM) were assessed. The expression of invadopodia proteins were analysed in comparison to normal tissue (OM) and correlated to different clinical-stage and histological grade of OSCC.

Results: TKs5, cortactin, TKs4 and MT1-MMP were significantly overexpressed in OSCC when compared to OM (p < 0.0001). Among tumour stages, TKs5 showed a statistical difference in immunolabelling between stage I and III (p = 0.026). Cortactin immunolabelling was statistically higher in grade I than in grade II and III. No differences were seen on TKs4 expression based on tumour staging or grading. MT1-MMP was higher expressed and showed statistical difference between stages I and III and grades I compared to II and III.

Conclusions: The invadopodia related-proteins were found to be overexpressed in OSCC when compared to OM, suggesting invadopodia formation and activity. Besides overexpressed in OSCC, cortactin, TKs4 and TKs5 showed no or ambiguous differences in protein expression when compared among clinical-stages or histological grades groups. Conversely, the expression of MT1-MMP increased in advanced stages and less differentiated tumours, suggesting MT1-MMP expression as a promising prognostic marker in OSCC.

Keywords: Immunohistochemistry; Invadopodia; Neoplasm Invasiveness; Oral squamous cell carcinoma; Pathology.

Publication types

  • Observational Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Vesicular Transport / analysis
  • Biomarkers, Tumor / analysis*
  • Cortactin / analysis
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 14 / analysis*
  • Middle Aged
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / pathology
  • Neoplasm Grading
  • Neoplasm Staging
  • Podosomes / enzymology*
  • Podosomes / pathology
  • Squamous Cell Carcinoma of Head and Neck / enzymology*
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Biomarkers, Tumor
  • CTTN protein, human
  • Cortactin
  • SH3PXD2A protein, human
  • SH3PXD2B protein, human
  • MMP14 protein, human
  • Matrix Metalloproteinase 14