TY - JOUR
T1 - Activation of matrix metalloproteinase-2 in head and neck squamous cell carcinoma
T2 - Studies of clinical samples and in vitro cell lines co-cultured with fibroblasts
AU - Tokumaru, Yutaka
AU - Fujii, Masato
AU - Otani, Yoshihide
AU - Kameyama, Kaori
AU - Imanishi, Yorihisa
AU - Igarashi, Naoki
AU - Kanzaki, Jin
N1 - Funding Information:
We are grateful to Dr Yasunori Okada, Professor at the Department of Pathology, Keio University, and Dr Jeffrey S. Humphrey, an active member of ASCO, Bristol-Myers Squibb, for their careful review of the manuscript. We also thank Dr Atsushi Suzuki and Naoko Hida for technical assistance. This work was supported by a Grant-in-Aid (08771432) for scientific research from the Ministry of Education, Science and Culture of Japan.
PY - 2000/3/13
Y1 - 2000/3/13
N2 - We undertook this present study to investigate the activation of matrix metalloproteinase-2 (MMP-2) in human head and neck squamous cell carcinomas (HNSCC) tissues and cell lines. Gelatinolytic activities of active MMP-2 were significantly higher in carcinoma samples than in normal portions. Furthermore, the activation ratio of proMMP-2 significantly correlated with cervical lymph node metastasis. In vitro studies revealed an HNSCC cell line, HEp-2, to produce neither the pro form nor the active form of MMP-2, but human fibroblasts were found to produce proMMP-2. However, coculture of HEp-2 cells with fibroblasts resulted in the production of not only proMMP-2 but also activeMMP-2 in the culture medium. Northern blot analysis revealed a stronger expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), which is a specific activator of MMP-2, mRNA in HEp-2 cells than in fibroblasts. These results suggest the activation of proMMP-2 as an important event in the process of HNSCC metastasis. They also suggest MMP-2 is secreted in its pro form by stromal fibroblasts surrounding the cancer cells and activated by MT1-MMP localized on the cancer cells. (C) 2000 Elsevier Science Ireland Ltd.
AB - We undertook this present study to investigate the activation of matrix metalloproteinase-2 (MMP-2) in human head and neck squamous cell carcinomas (HNSCC) tissues and cell lines. Gelatinolytic activities of active MMP-2 were significantly higher in carcinoma samples than in normal portions. Furthermore, the activation ratio of proMMP-2 significantly correlated with cervical lymph node metastasis. In vitro studies revealed an HNSCC cell line, HEp-2, to produce neither the pro form nor the active form of MMP-2, but human fibroblasts were found to produce proMMP-2. However, coculture of HEp-2 cells with fibroblasts resulted in the production of not only proMMP-2 but also activeMMP-2 in the culture medium. Northern blot analysis revealed a stronger expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), which is a specific activator of MMP-2, mRNA in HEp-2 cells than in fibroblasts. These results suggest the activation of proMMP-2 as an important event in the process of HNSCC metastasis. They also suggest MMP-2 is secreted in its pro form by stromal fibroblasts surrounding the cancer cells and activated by MT1-MMP localized on the cancer cells. (C) 2000 Elsevier Science Ireland Ltd.
KW - Fibroblast
KW - Head and neck carcinoma
KW - Matrix metalloproteinase-2
KW - Membrane-type 1 matrix metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=0034089749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034089749&partnerID=8YFLogxK
U2 - 10.1016/S0304-3835(99)00371-7
DO - 10.1016/S0304-3835(99)00371-7
M3 - Article
C2 - 10755382
AN - SCOPUS:0034089749
SN - 0304-3835
VL - 150
SP - 15
EP - 21
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
