Tissue-Type plasminogen activator (tPA) in breast cancer: relationship with clinicopathological parameters and prognostic significance

Corte, M.D.; P, Vérez; Rodrı́guez, Juan Carlos; Roibás, Antonio; Dominguez, Mariana; Lamelas, Marı́a L.; Vázquez, Julio; Muñiz, J.L.; Allende, M.T.; González, Luis O.; Fueyo, Antonio; Vizoso, F

doi:10.1007/s10549-004-2624-x

Cited by 22 publications

(19 citation statements)

References 31 publications

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“…Nevertheless, there are several unknown aspects on the role of HA in breast cancer. Thus, it is remarkable that in the present study we found, in addition to the finding of a positive relationship between HA and ER, a unexpected positive relationship between HA content and those of well-known estrogen-inducible proteins in breast cancer cells, such as PR [44], pS2 [45,46], tPA [47][48][49], which are also associated with a good prognosis in breast cancer [50][51][52][53][54][55][56]. These findings led us to consider that the estrogens might to modulate the HA expression in breast cancer.…”

Section: Discussionsupporting

confidence: 61%

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Corte

González

Lamelas

et al. 2006

Breast Cancer Res Treat

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Section: Discussionsupporting

confidence: 61%

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Corte

González

Lamelas

et al. 2006

Breast Cancer Res Treat

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“…One study showed that tPA expression in breast cancer is not associated with the malignant or benign state [52]. Another report states that low intratumoral tPA expression levels correlate with aggressiveness and poor prognosis for breast cancer patients [53]. Irrespective of these reports, increased PDGF-C expression and serine protease-mediated proteolytic activation of PDGF-C in human breast carcinoma MCF7 cells resulted in fibroblast migration in a paracrine manner as well as increased MCF7 cell proliferation and anchorage independent growth in an autocrine manner.…”

Section: Discussionmentioning

confidence: 99%

Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression

Hurst

Najy

Ustach

et al. 2012

Biochemical Journal

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The PDGF family members are potent mitogens for cells of mesenchymal origin and serve as important regulators of cell migration, survival, apoptosis, and transformation. Tumor-derived PDGF ligands are thought to function in both autocrine and paracrine manners, activating receptors on tumor and surrounding stromal cells. PDGF-C and -D are secreted as latent dimers, unlike PDGF-A and -B. Cleavage of the CUB domain from the PDGF-C and -D dimers is required for their biological activity. At present, little is known about the proteolytic processing of PDGF-C, the rate-limiting step in the regulation of PDGF-C activity. Here we show that the breast carcinoma cell line, MCF7, engineered to overexpress PDGF-C, produces proteases capable of cleaving PDGF-C to its active form. Increased PDGF-C expression enhances cell proliferation, anchorage independent cell growth, and tumor cell motility by autocrine signaling. In addition, MCF7-produced PDGF-C induces fibroblast cell migration in a paracrine manner. Interestingly, PDGF-C enhances tumor cell invasion in the presence of fibroblast, suggesting a role of tumor-derived PDGF-C in tumor-stromal interactions. In the present study, we identify tissue plasminogen activator (tPA) and matriptase as major proteases for processing of PDGF-C in MCF7 cells. In in vitro studies, we also show that urokinase plasminogen activator (uPA) is able to process PDGF-C. Furthermore, by site-directed mutagenesis, we identify the cleavage site for these proteases in PDGF-C. Lastly, we provide evidence suggesting a 2-step proteolytic processing of PDGF-C involving creation of a hemidimer, followed by growth factor domain dimer (GFD-D) generation.

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“…There are many studies reporting overexpression of some genes known to be associated with invasiveness and aggressiveness in estrogen negative tumors e.g. HER-2 neu, EGF, mutant P53 [27,28] High uPA (urokinase plasminogen activator) and type 1 plasminogen activator (PAI-1) was found to be associated with shorter recurrence-free survival and ER and PgR negativity [29]. Rodrigues et al reported that Cathepsin D expression was higher in ER and PgR-positive than in hormone receptor negative tumors [30].…”

Section: Discussionmentioning

confidence: 99%

Long-term pattern of disease recurrence among patients with early-stage breast cancer according to estrogen receptor status and use of adjuvant tamoxifen

Khoshnoud

Fornander

Johansson

et al. 2007

Breast Cancer Res Treat

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The results showed that the mentioned substantial differences in terms of gene expression appeared mainly to be related to endocrine sensitivity and not to metastatic potential. However, a slight advantage during the first five years for the ER positive versus ER negative patients in terms of cumulative incidence of events, suggested that ER negativity in some cases is correlated with an increased tumour growth rate.

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Tissue-Type plasminogen activator (tPA) in breast cancer: relationship with clinicopathological parameters and prognostic significance

Abstract: The results of the present investigation indicate that low intratumoral tPA levels are associated with aggressiveness and poor prognosis in breast cancer patients. However, the study suggests that tPA levels do not predict response to systemic adjuvant therapy.

Cited by 22 publications

References 31 publications

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression

Long-term pattern of disease recurrence among patients with early-stage breast cancer according to estrogen receptor status and use of adjuvant tamoxifen

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