Activation of EDTA-resistant gelatinases in malignant human tumors

Giulio Ghersi, Yuhuan Qiao, Naoko Hirashima, Ah-Kau Ng, Tetsu Yamane, Jahn M. Nesland, Qiang Zhao, Yoshiyuki Mori, Qiang Zhao, Wei Zeng, Wen-Tien Chen, Mengzhen Zhang, Qiang Zhao, Masako Mitsumata, Michael Pearl, Zhenhe Suo, Alanna Kennedy, Donghai Chen, Jaw-Yuan Wang

Risultato della ricerca: Articlepeer review

29 Citazioni (Scopus)

Abstract

Among the many proteases associated with human cancer, seprase or fibroblast activation protein alpha, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody- or lectin-affinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion.
Lingua originaleEnglish
pagine (da-a)9977-9985
Numero di pagine9
RivistaCancer Research
Volume66
Stato di pubblicazionePublished - 2006

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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