Role of monocyte‐lineage cells in prostate cancer cell invasion and tissue factor expression

Lindholm, Paul F.; Lü, Yi; Adley, Brian P.; Vladislav, Tudor; Jovanovic, Borko; Sivapurapu, Neela; Yang, Ximing J.; Kajdacsy-Balla, André

doi:10.1002/pros.21202

Cited by 27 publications

(23 citation statements)

References 70 publications

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“…It has been found that TF/FVIIa involves in cleaving and activating G-proteincoupled PAR2, which further triggers downstream signaling pathways in cancer cells [22,23]. There are growing evidences that TF and PAR2 are overexpressed in a wide range of tumor types, such as breast, colon, prostate, and hepatocellular cancers, and play crucial roles in promoting cell growth and migration [8,[24][25][26][27]. It has been reported that TF/FVIIa/PAR2 axis induces anti-apoptotic protein Birc 3 and prevents apoptosis and cell death of breast cancer [28,29].…”

Section: Discussionmentioning

confidence: 99%

Involvement of ERK1/2/NF-κB signal transduction pathway in TF/FVIIa/PAR2-induced proliferation and migration of colon cancer cell SW620

Guo

Zhou

et al. 2011

Tumor Biol.

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Our previous study has demonstrated that TF/FVIIa and protease-activated receptor 2 (PAR2) are closely related to the proliferation and migration of colon cancer cell line SW620. However, the detailed signaling cascades and underlying molecular mechanisms remain unclear. This study has investigated whether extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor kappaB (NF-κB) signaling pathways are involved in the events. The results revealed that PAR2-activating peptide (PAR2-AP) or FVIIa elicited time-dependent upregulation of ERK1/2 phosphorylation in SW620 cells, and the effect of FVIIa was significantly attenuated by anti-TF antibody. PAR2-AP or FVIIa also increased NF-κB (p65/RelA) levels among cell nuclear proteins and simultaneously decreased IκB-α levels in the cytoplasmic proteins. Such effects of FVIIa can be inhibited with anti-PAR2 or anti-TF antibodies. While ERK1/2 inhibitor (U0126) intervened with the regulatory effects of PAR2-AP and FVIIa on IκB-α/NF-κB (p65/Rel) expression in the cells, NF-κB inhibitor (PDTC) partially blocked the enhancing effects of PAR2-AP and FVIIa on the proliferating and migratory ability of SW620 cells. Furthermore, the regulatory effects of PAR2-AP and FVIIa on expressions of certain proteins (IL-8, caspase-7, and TF) were also significantly abolished by PDTC. Collectively, the data in this study suggest that the interaction between FVIIa and TF induces PAR2 activation, thereby triggers the ERK1/2 and IκB-α/NF-κB signal transduction pathway to regulate the gene expression of IL-8, TF, and caspase-7, and ultimately promotes SW620 cell proliferation and migration.

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Section: Discussionmentioning

confidence: 99%

Involvement of ERK1/2/NF-κB signal transduction pathway in TF/FVIIa/PAR2-induced proliferation and migration of colon cancer cell SW620

Guo

Zhou

et al. 2011

Tumor Biol.

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“…The density, size, and location of tumor infiltrating macrophages in prostate cancer were reported as powerful predictors of patient outcome (11) and prostate cancer specimens harbor increased positive cells expressing the macrophage specific marker CD68 compared to benign glands (12). More recently, it was demonstrated that expression of macrophage colony-stimulating factor (M-CSF) and its receptor colony-stimulating factor-1 receptor (CSF-1R) are increased in primary tumors of patients exhibiting metastatic disease (13), although other studies have demonstrated variable evidence for TAMs during prostate cancer progression (11-12, 14-15). …”

Section: Introductionmentioning

confidence: 99%

Macrophage-Dependent Cleavage of the Laminin Receptor α6β1 in Prostate Cancer

Sroka

Sandoval

Chopra

et al. 2011

Molecular Cancer Research

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The laminin binding integrin α6β1 plays a major role in determining the aggressive phenotype of tumor cells during metastasis. Our previous work has shown that cleavage of the α6β1 integrin to produce the structural variant α6pβ1 on tumor cell surfaces is mediated by the serine protease uPA. Cleavage of α6β1 increases tumor cell motility, invasion, and prostate cancer metastasis, and blockage of uPA inhibits α6pβ1 production. In human tumors uPA and uPAR are expressed in tumor cells and tumor associated macrophages (TAMs). TAMs localize to solid tumors and contribute to increased tumor growth and the metastatic phenotype. In our present study, we utilized a co-culture system of PC-3 prostate tumor cells and macrophages (12-O-tetradecanoylphorbol-13-acetate (TPA) differentiated human leukemia HL-60 cells) to investigate the hypothesis that macrophages stimulate the production of the pro-metastatic variant α6pβ1 on human prostate cancer cells via the uPA/uPAR axis. Our results indicate that adherent macrophages co-cultured with PC-3 cells increased PC-3 uPAR mRNA, uPAR cell-surface protein expression and α6 integrin cleavage. The stimulation does not require macrophage/tumor cell contact since macrophage conditioned medium is sufficient for increased uPAR transcription and α6 cleavage dependent PC-3 cell invasion. The increased cleavage was dependent on uPAR since production was blocked by silencing RNA targeting uPAR. These results indicate that macrophages can stimulate uPA/uPAR production in tumor cells which results in α6 integrin cleavage. These data suggest that tumor associated macrophages promote pro metastatic integrin dependent pericellular proteolysis.

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“…The up-regulation of TF is a characteristic of malignant cells, and higher TF expression has been associated with increased angiogenesis, metastasis and a poor prognosis in solid cancers such as pancreatic and ovarian cancer [25]–[30]. Studies in prostate cancer have also shown that TF expression was significantly higher in prostate cancer cells than benign prostatic epithelium and correlates significantly with Gleason score and stage of disease, the expression of VEGF-A, higher micro-vessel density, bone metastases and poor survival [11], [31]–[33]. These observations support the hypothesis that thromboembolic disease is more than an epiphenomenon in patients with cancer and that the clinical hypercoagulable state may be a surrogate for an aggressive tumor phenotype.…”

Section: Discussionmentioning

confidence: 99%

Symptomatic and Incidental Venous Thromboembolic Disease Are Both Associated with Mortality in Patients with Prostate Cancer

et al. 2014

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IntroductionThe association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer.MethodsData regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR).ResultsAt diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29–11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co-morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE.ConclusionVenous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population.

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Role of monocyte‐lineage cells in prostate cancer cell invasion and tissue factor expression

Abstract: This study shows that co-culture with monocyte-lineage cells induced prostate cancer cell invasion activity. PC-3 invasion and TF expression was induced in co-culture with U-937 cells and partially inhibited with TF neutralizing antibodies.

Cited by 27 publications

References 70 publications

Involvement of ERK1/2/NF-κB signal transduction pathway in TF/FVIIa/PAR2-induced proliferation and migration of colon cancer cell SW620

Involvement of ERK1/2/NF-κB signal transduction pathway in TF/FVIIa/PAR2-induced proliferation and migration of colon cancer cell SW620

Macrophage-Dependent Cleavage of the Laminin Receptor α6β1 in Prostate Cancer

Symptomatic and Incidental Venous Thromboembolic Disease Are Both Associated with Mortality in Patients with Prostate Cancer

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