MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells - PubMed (original) (raw)

MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells

H Pulyaeva et al. Clin Exp Metastasis. 1997 Mar.

Erratum in

Clin Exp Metastasis 1997 May;15(3):338

Abstract

We have previously reported that human breast carcinoma (HBC) cell lines expressing the mesenchymal intermediate filament protein vimentin (VIM+) are highly invasive in vitro, and highly metastatic in nude mice when compared to their VIM- counterparts. Since only VIM+ cell lines can be induced to activate matrix metalloproteinase-2 (MMP-2) upon stimulation with Concanavalin A (Con A), we have examined here membrane type 1 MMP (MT1-MMP), a cell surface activator of MMP-2. Northern analysis reveals baseline expression of MT1-MMP in five of the six VIM+ cell lines studied (MDA-MB-231, MDA-MB-435, BT-549, Hs578T, MCF-7(ADR)), each of which showed variable activation of exogenous MMP-2 after treatment with Con A. In contrast, the four VIM-, poorly invasive HBC cell lines studied (MCF-7, T47D, MDA-MB 468, ZR-75-1) lacked baseline MT1-MMP mRNA expression, and showed no induction of either MT1-MMP expression or MMP-2-activation with Con A. Such differential MT1-MMP expression was confirmed in vivo using in situ hybridization analysis of nude mouse tumor xenografts of representative cell lines. Western analysis of the MDA-MB-231 cells revealed baseline membrane expression of a 60 kDa species, which was strongly induced by Con A treatment along with a weaker band co-migrating with that from MT1-MMP-transfected COS-1 cells (63 kDa), presumably representing latent MT1-MMP. MT1-MMP immunofluorescence strongly decorated Con A-stimulated MDA-MB-231 cells in a manner consistent with membranous staining, but did not decorate the unstimulated MDA-MB-231 cells or MCF-7 cells under either condition. Collectively, the results suggest the constitutive production of active MT1-MMP which is unavailable for either MMP-2 activation or immuno-decoration until Con A treatment. Since VIM expression arises by virtue of the so-called epithelial to mesenchymal transition (EMT) in invasive embryonic epithelia, we propose that this represents a major metastasis mechanism in breast carcinomas. MT1-MMP on the surface of such 'fibroblastoid' carcinoma cells may mediate a paracrine loop for the utilization of stromally produced MMP-2, and contribute to the poorer survival associated with VIM+ breast carcinomas.

PubMed Disclaimer

Cited by

Collagen and Discoidin Domain Receptor 1 Partnership: A Multifaceted Role in the Regulation of Breast Carcinoma Cell Phenotype.
Saby C, Maquoi E, Saltel F, Morjani H. Saby C, et al. Front Cell Dev Biol. 2021 Dec 22;9:808625. doi: 10.3389/fcell.2021.808625. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 35004699 Free PMC article. Review.
Collection on reports of molecules linked to epithelial-mesenchymal transition in the process of treating metastasizing cancer: a narrative review.
Cai Y, Wang B, Li B, Huang X, Guo H, Liu Y, Chen B, Zhao S, Wu S, Li W, Wang L, Jia K, Wang H, Chen P, Jiang M, Tang X, Qi H, Dai C, Ye J, He Y. Cai Y, et al. Ann Transl Med. 2021 Jun;9(11):946. doi: 10.21037/atm-20-7002. Ann Transl Med. 2021. PMID: 34350261 Free PMC article. Review.
Matrix stiffness primes lymphatic tube formation directed by vascular endothelial growth factor-C.
Alderfer L, Russo E, Archilla A, Coe B, Hanjaya-Putra D. Alderfer L, et al. FASEB J. 2021 May;35(5):e21498. doi: 10.1096/fj.202002426RR. FASEB J. 2021. PMID: 33774872 Free PMC article.
Matrix metalloproteinase 2 contributes to aggressive phenotype, epithelial-mesenchymal transition and poor outcome in nasopharyngeal carcinoma.
Li S, Luo W. Li S, et al. Onco Targets Ther. 2019 Jul 17;12:5701-5711. doi: 10.2147/OTT.S202280. eCollection 2019. Onco Targets Ther. 2019. PMID: 31410017 Free PMC article.
Cutting to the Chase: How Matrix Metalloproteinase-2 Activity Controls Breast-Cancer-to-Bone Metastasis.
Tauro M, Lynch CC. Tauro M, et al. Cancers (Basel). 2018 Jun 5;10(6):185. doi: 10.3390/cancers10060185. Cancers (Basel). 2018. PMID: 29874869 Free PMC article. Review.

References

1. Virchows Arch. 1994;424(6):641-5 - PubMed
1. Mod Pathol. 1991 Mar;4(2):239-46 - PubMed
1. Breast Cancer Res Treat. 1993;24(3):241-55 - PubMed
1. J Cell Physiol. 1992 Mar;150(3):534-44 - PubMed
1. Kidney Int. 1993 Jan;43(1):163-70 - PubMed

MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells - PubMed (original) (raw)