Metastasis suppressor proteins in cutaneous squamous cell carcinoma

Pathol Res Pract. 2016 Jul;212(7):608-15. doi: 10.1016/j.prp.2015.12.018. Epub 2016 May 6.


Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.

Keywords: A-431; HaCaT; Metastasis suppressor proteins; Skin; Squamous cell carcinoma.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Tumor Suppressor Proteins / metabolism*


  • Biomarkers, Tumor
  • Cadherins
  • Tumor Suppressor Proteins