Proteolytic degradation of extracellular matrix in tumor invasion

Tryggvason, Karl; Höyhtyä, Matti; Salo, Tuula

doi:10.1016/0304-419x(87)90006-0

Cited by 293 publications

(213 citation statements)

References 185 publications

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“…After the primary tumor has established itself in the mucosa, the first step in the mechanism of cancer metastasis is breach of the basement membrane [153,171]. The basement membrane is composed primarily of type IV collagen, which forms the structural scaffolding of the basement membrane, laminin, and proteoglycans.…”

Section: Discussionmentioning

confidence: 99%

“…As a lymph node is progressively replaced by metastatic tumor, the local lymphatic flow may be distorted, reflected and perhaps reversed, directing new lymph borne tumor cells to fresh nodes. The cancerous node itself may act as a focus for further tertiary spread [28,153]. The blood circulation (blood more so than lymph) is a hostile environment for cancer cells, and most cells released into the circulation die before they successfully exit the circulation [28].…”

Section: Discussionmentioning

confidence: 99%

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A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

et al. 2011

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“…However, although the evaluation of the treated cells by flow cytometry or by the sulforhodamine B test often showed an increase of cell proteins, the possibility of the selective inhibition of focal Experimental Therapeutics protein synthesis can not be excluded. MMP-2 secretion involves the degradation of type IV, V, VII and X collagens and fibronectin (Mullins and Rohrlich, 1983) which are constituents of both the basement membrane and the interstitial stroma (Tryggvason et al, 1987). This degradation facilitates the intrusion of endothelial cells across such structures, an important step for neovessel sprouting (Mullins and Rohrlich, 1983;Tryggvason et al, 1987) and metastasis formation (Tryggvason et al, 1987;Mignatti and Rifkin, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…MMP-2 secretion involves the degradation of type IV, V, VII and X collagens and fibronectin (Mullins and Rohrlich, 1983) which are constituents of both the basement membrane and the interstitial stroma (Tryggvason et al, 1987). This degradation facilitates the intrusion of endothelial cells across such structures, an important step for neovessel sprouting (Mullins and Rohrlich, 1983;Tryggvason et al, 1987) and metastasis formation (Tryggvason et al, 1987;Mignatti and Rifkin, 1993). Also, previous results by this group showed the inhibition of mRNAs for MMP-2, specularly to the increase of the mRNA for TIMP-2, to be associated to enhanced deposition of extracellular matrix within the tumour, increased thickness of the capsule surrounding it and appearance of a more defined wall around tumour blood vessels (Sava et al, 1996); all these events were matched to a marked reduction of the formation of spontaneous metastases.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

et al. 2002

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NAMI-A is a ruthenium-based compound with selective anti-metastasis activity in experimental models of solid tumours. We studied whether this activity was dependent on anti-angiogenic ability of NAMI-A. We thus investigated its in vitro effects on endothelial cell functions necessary for angiogenesis to develop, as well as its in vivo effects in the chick embryo chorioallantoic membrane model. Endothelial cell proliferation, chemotaxis, and secretion of the matrix-degrading enzyme metalloproteinase-2 were inhibited by NAMI-A in a dose-dependent manner, and without morphologic signs of cell apoptosis or necrosis. Lastly, NAMI-A displayed a dose-dependent in vivo anti-angiogenic activity in the chorioallantoic membrane model. These data suggest that the anti-angiogenic activity of NAMI-A can contribute to its anti-metastatic efficacy in mice bearing malignant solid tumours.

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“…Serine proteases serve several functions during tumour progression, including stimulating cellular growth, angiogenesis as well as degradation of extracellular matrix ( Tryggvason et al, 1987;Duffy, 1991;Liotta et al, 1991). In particular, the last function is thought to be critical in conferring the invasiveness and metastatic potential of cancer cells (Hanahan and Weinberg, 2000).…”

mentioning

confidence: 99%

Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer

et al. 2001

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Summary Kallikrein gene 5 (KLK5, also known as KLK-L2), located on chromosome 19q13.4, is one of the newly identified members of the kallikrein gene family, which is a subgroup of the serine protease enzyme family. In normal human tissues, KLK5 is highly expressed in skin, mammary gland and testis. Preliminary RT-PCR analysis has indicated that KLK5 is expressed in a subset of ovarian tumours. We have thus hypothesized that KLK5 may be a new prognostic indicator in ovarian cancer. We have examined the mRNA expression of KLK5 in 142 malignant ovarian tissues. Tumours were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK5 was amplified by PCR using gene specific primers, and the identity of the PCR product was verified by sequencing. Ovarian tissues were then classified as KLK5 positive or negative, based on ethidium bromide staining of the PCR product on agarose gels. KLK5 was found to be highly expressed in 58/142 (41%) of ovarian cancer samples while its level of expression was very low in normal ovarian tissues. We found a strong positive relation between KLK5 expression and tumour grade (P = 0.006) and disease stage (P = 0.027). Univariate survival analysis revealed that patients with ovarian tumours positive for KLK5 expression had an increased risk for relapse and death (P = 0.018 and 0.022, respectively). In multivariate analysis, KLK5 expression showed independent prognostic value only in the subset of tumours with lower grade disease (grades I and II). We conclude that KLK5 expression is associated with more aggressive forms of epithelial ovarian carcinoma and has indepdent prognostic value in low grade tumours. 643-650 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1649, available online at http://www.idealibrary.com on http://www.bjcancer.comIn the present study, we have evaluated KLK5 mRNA expression in relation to patient survival and other clinicopathologic variables in epithelial ovarian carcinoma. Our results demonstrate that KLK5 is an independent prognostic marker of poor prognosis in a subset of patients with grade I/II tumours. MATERIALS AND METHODS Ovarian cancer specimens and patients142 consecutive patients with epithelial ovarian carcinoma were included in this study, with ages ranging from 25 to 80 with a median of 59 years. Patients underwent surgery and treatment for primary ovarian carcinoma at the Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Turin, Italy between July, 1991 and April, 1999. Follow-up information (median follow-up period 48 months) was available for 138 patients, among whom 83 (60%) have relapsed and 55 (40%) died. Of the 142 ovarian adenocarcinomas, for which histological diagnosis was available, 64 (45%) were serous papillary, 26 (18%) endometrioid, 22 (16%) undifferentiated, 12 (8%) clear cell, 11 (8%) mucinous, 6 (4%) Mullerian and 1 (1%) was unclassified. Due to the relatively small sample size, the clear cell, mucinous and Mullerian types were combined into one category...

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Proteolytic degradation of extracellular matrix in tumor invasion

Cited by 293 publications

References 185 publications

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer

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