Role of secreted protein acidic in hematogenous metastasis of gastric cancer

Eur Rev Med Pharmacol Sci. 2017 Oct;21(19):4311-4321.

Abstract

Objective: To investigate tumor microenvironment of metastasis (TMEM) and the expression of SPARC (secreted protein acidic and rich in cysteine) in gastric cancer, and their relationships with hematogenous metastasis.

Patients and methods: Twenty-six pairs of cases with gastric cancer were enrolled, in which there were 26 cases with distant organ metastases and 26 cases of gastric cancer without organ metastases as controls. TMEM (by double-stained immunohistochemistry) and the expression of SPARC were determined in twenty-six pairs of cases. In addition, we selected 48 patients to detect the expression of SPARC, VEGF (vascular endothelial growth factor), and evaluated TAMs (tumor associated macrophages), MVD (the microvessel density), MPI (microvessel pericyte coverage index), and TMEM in gastric cancer tissues by immunohistochemistry.

Results: TMEM count was significantly higher in the metastatic gastric cancer tissues than that in non-metastatic cancer tissues in a case-control study (p<0.01). On the contrary, SPARC expression was lower in the metastatic gastric cancer tissues than that in non-metastatic cancer tissues. TMEM count, TAMs, and MVD were significantly correlated with invasion depth, histological type and TNM stage (p<0.05 or p<0.01). Expression of SPARC and VEGF were significantly correlated with tumor histological types, invasion depth, differentiation and lymph node metastasis of patients (p<0.05). SPARC and VEGF expression in stromal cells of gastric cancer tissues were significantly correlated with TAMs, MVD and MPI (p<0.05). In addition, SPARC expression was significantly inversely correlated with VEGF expression in gastric cancer tissues (p<0.05).

Conclusions: TMEM was detected in initial gastric cancer resection and closely correlated with hematogenous metastasis. Furthermore, SPARC may be involved in gastric cancer metastasis by effecting on tumor microenvironment.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Hematologic Neoplasms / etiology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Osteonectin / genetics
  • Osteonectin / metabolism*
  • Stomach Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Osteonectin
  • SPARC protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A