Abstract
We aimed to clarify the prime role of recurrence in stage I lung cancer. To determine the expression profiles, quantitative RT–PCR and real-time PCR were performed subsequently to evaluate the validity of meaningful molecules identified by 0.12 K c-DNA array experiment surveys. In all, 10 lung cancer patients presenting with recurrence of stage IB were selected and compared with 10 stage IB lung cancer patients without recurrence since biopsied 3 years previously. On c-DNA microarray data analysis using pairs of recurred and the corresponding nonrecurred patients, the following genes were found to be upregulated in the recurred cases: matrix metalloproteinase (MMP)-10 in five cases, MMP-12 in two cases, MMP-11, MMP-14, MMP-15, fos, cyclin E2, E2F3, TGF-α in each one case. The most frequently upregulated genes in recurred lung cancers were MMP-10 (stromelysin-2) and MMP-12 (macrophage elastase). On transcriptional assay by quantitative RT–PCR and real-time RT–PCR analysis to validate those molecules, both transcripts of MMP-10 and MMP-12 were significantly more upregulated in recurred stage IB lung cancer than in the non-recurred stage IB lung cancer (P=0.004). Transcript levels were identical to c-DNA array data. The protein levels of these entities were also evaluated by immunohistochemistry of archival slides. By immunohistochemistry, MMP-10 monoclonal antibody showed more intense immunoreactivity in the recurred stage IB lung cancer than in the nonrecurred stage IB lung cancer (P=0.0313). Our approach revealed that MMP-10 plays an important role in the recurrence in stage IB lung cancer, irrespective of the histologic type.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bolon I, Devouassoux M, Robert C, Moro D, Brambilla C and Brambilla E . (1997). Am. J. Pathol., 150, 1619–1629.
Brown PD, Bloxidge RE, Stuart NSA, Gatter KC and Carmichael J . (1993). J. Natl. Cancer Inst., 85, 574–578.
Cai M, Onoda K, Takao M, Kyoko I, Shimpo H, Yoshida T and Yada I . (2002). Clin. Cancer Res., 8, 1152–1156.
Carmeleit P, Moons L, Lijnen Rn, Crawley J, Tipping P, Drew A, Eeckhout Y, Shapiro SD, Lupu F and Collen D . (1997). Nat Genet, 17, 439–444.
Chambers AF and Matrisian LM . (1997). J. Natl. Cancer Inst., 89, 1260–1270.
Curran S and Murray GI . (2000). Eur. J. Cancer, 36, 1621–1630.
Delebecq TJ, Porte H, Zerimech F, Copin M, Gouyer V, Dacquembronne E, Balduyck M, Wirtz A and Huer G . (2000). Clin. Cancer Res., 6, 1086–1092.
Fong KM, Kida Y, Zimmerman PV and Smith PJ . (1996). Clin. Cancer Res., 2, 1369–1372.
Hautamaki RD, Kobayashi DK, Senior RM and Shapiro SD . (1997). Science, 277, 2002–2004.
Kerkela E, Jeskanen L, Lohi J, Grenman R, Kahari VM and Saarialho-Kere U . (2001). Br. J. Cancer, 84, 650–669.
Langmann T, Mauerer R, Zahn A, Moehle C, Probst M, Stermmel W and Schmitz G . (2003). Clin. Chem., 49, 230–238.
Martini N, Bains MS, Burt ME, Zakowski MF, Mocormack P, Rusch VW and Ginberg RJ . (1995). J. Thorac. Cardiovasc. Surg., 109, 120–129.
Martini N and Beattic Jr EJ . (1977). J. Thorac. Cardiovasc. Surg., 74, 499–505.
Muller D, Breathnach R, Millon R, Bronner G, Flesch H, Dumont P, Eber M and Abecassis J . (1991). Int. J. Cancer, 48, 550–556.
Murray GI . (2001). J. Pathol., 195, 135–137.
Nagakawa H and Yagihashi S . (1994). Jpn. J. Cancer Res., 85, 934–938.
Nagase H (ed). (1998). Stromelysin 1 and 2. Matrix Metalloproteinases, Parks WC and Mecham RP (eds). Academic Press: San Diego, pp. 43–84.
Nawrocki B, Polette M, Marchand V, Monteau M, Gillery P, Tournier JM and Birembaut P . (1997). Int. J. Cancer, 72, 556–564.
Ohori P, Yousem SA, Griffin J, Stanis K, Stetler-Stevenson WG, Colby TV and Somez-Alpan E . (1992). Am. J. Surg. Pathol., 16, 675–686.
Passlick B, Sienel W, Seen-Hibler R, Wockel W, Thetter O, Mutschler W and Pantel K . (2000). Clin. Cancer Res., 6, 3944–3948.
Rechardt O, Elomaa O, Vaalamo M, Paakkonen K, Jahkola T, Hook-Nikane J, Hembry RM, Hakkinen L, Kere J and Saarialho-Kere U . (2000). J. Invest. Dermatol., 115, 778–787.
Shapiro SD and Senior RM . (1998). Macrophage Elastase: Matrix Metalloproteinases, Parks WC Mecham RP (eds). Academic Press: San Diego, pp. 185–197.
Soini Y, Paakko P and Autio-Harmainen H . (1993). Am. J. Pathol., 142, 1622–1630.
Sreenath T, Matrisian LM, Stetler-Stevenson W, Gattoni-Celli S and Pozzatti RO . (1992). Cancer Res., 52, 4942–4947.
Thomas P, Khokha R, Shepherd FA, Feld R and Tsao M . (2000). J. Pathol., 190, 150–156.
Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y and Seiki M . (1995). Int. J. Cancer, 64, 355–359.
Urbanski SJ, Edwards DR, Maitland A, Leco KJ, Watson A and Kossakowska AE . (1992). Br. J. Cancer, 66, 1188–1194.
Acknowledgements
This study was financially supported by a faculty research grant (CMB-YUHAN 2002-02) of Yonsei University College of Medicine for 2002 [NHC & SHC]. This study was supported by BK 21 project for Medical Science, Yonsei University [NHC].
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cho, N., Hong, K., Hong, S. et al. MMP expression profiling in recurred stage IB lung cancer. Oncogene 23, 845–851 (2004). https://doi.org/10.1038/sj.onc.1207140
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1207140
Keywords
This article is cited by
-
Blocking MMP-12-modulated epithelial-mesenchymal transition by repurposing penfluridol restrains lung adenocarcinoma metastasis via uPA/uPAR/TGF-β/Akt pathway
Cellular Oncology (2021)
-
Transcriptional induction of MMP-10 by TGF-β, mediated by activation of MEF2A and downregulation of class IIa HDACs
Oncogene (2010)
-
Serum bone turnover markers may be involved in the metastatic potential of lung cancer patients
Medical Oncology (2010)
-
Matrix metalloproteinase-10 is a critical effector of protein kinase Cι-Par6α-mediated lung cancer
Oncogene (2008)
-
Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues
British Journal of Cancer (2005)