Autocrine Effects of Tumor-Derived Complement

Cho, Min Soon; Vásquez, Hernán; Rupaimoole, Rajesha; Pradeep, Sunila; Wu, Sherry Y.; Zand, Behrouz; Han, Hee Dong; Rodríguez-Aguayo, Cristian; Bottsford-Miller, Justin; Huang, Jie; Miyake, Takahito; Choi, Hyun-Jin; Dalton, Heather J.; Ivan, Cristina; Baggerly, Keith A.; López-Berestein, Gabriel; Sood, Anil K.; Afshar-Kharghan, Vahid

doi:10.1016/j.celrep.2014.02.014

Cited by 165 publications

(191 citation statements)

References 25 publications

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“…Thus, C5aR expression in UCC may correlate with the low survival rate exhibited by patients (Table II). It has been reported that high C5aR mRNA expression in cancer cells is associated with short survival time in patients with ovarian or lung cancer (24), in accordance with the results of the present study, which revealed that C5aR protein expression of UCC cells correlated with low survival rates in UCC patients ( Fig. 2; Table II).…”

Section: Discussionsupporting

confidence: 82%

“…Although it has not yet been demonstrated in human UCC, C5aR signaling suppresses apoptosis, induces T-cell expansion via the enhanced expression of Bcl-2 (32) and enhances neuronal cell survival via inhibition of caspase-3 activation (33). C5a is present in the cancer microenvironment (17,20,23), where, by stimulation with C5a, the apoptosis of C5aR-expressing UCC may be suppressed; this supression facilitates the growth and development of cancer in concert with the C5a-elicited enhancement of proliferation (24) and invasiveness (22). Thus, C5aR expression in UCC may correlate with the low survival rate exhibited by patients (Table II).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, direct C5a release from C5 by cell membrane proteases of cancer cells and promotion of C5aR-expressing cancer cell invasiveness by C5a was demonstrated, indicating that a self-activation circuit via C5aR exists in cancer cells that express C5aR and proteases on the cell surface (23). Notably, a previous study revealed that a C5aR agonist increased cancer cell proliferation and C5aR silencing reduced tumor growth (24). Thus, we hypothesize that C5aR-positive cancer cells are more aggressive than C5aR-negative cells and thus, C5aR expression in cancer cells may be associated with poor prognosis of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy

et al. 2016

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Abstract.Patients with aggressive urothelial cell carcinoma (UCC) that undergo radical cystectomy or nephroureterectomy exhibit markedly high rates of disease recurrence and mortality. To select appropriate adjuvant thxerapies in addition to radical surgery, the identification of predictive prognostic markers for UCC patients is required. The aim of the present study was to identify such markers, by evaluating the association of UCC complement component 5 (C5) fragment a (C5a) receptor (C5aR) expression, detected using immunohistochemistry, with clinicopathological parameters and survival outcomes of UCC patients. The results revealed that C5aR was expressed in cancer cells, particularly at the invasive front, but not in noncancerous urothelial cells or adjacent cells. The UCC C5aR-positive rate of patients treated with radical surgeries was 73% (38/52) and the rate was 83% (20/24) at stages I-II of disease. No correlation between C5aR expression and any of clinicopathological parameters, which included gender, tumor location, World Health Organization grade, T stage, vessel invasion and stage of disease, was identified. However, univariate and multivariate analyses revealed that C5aR-positive UCC patients exhibited significantly lower overall survival rates [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.03-9.60; P=0.035 and HR, 3.92; 95% CI, 1.15-13.4; P=0.029, respectively] and 5-year survival rates (0.42 vs. 0.83) compared with C5aR-negative UCC patients. Furthermore, 5-year survival and disease-specific survival rates were lower in patients with C5aR-positive UCC (0.51; 95% CI, 0.30-0.71) than patients with C5aR-negative UCC (0.83; 95% CI, 0.62-1.00). These results indicate that UCC C5aR expression is predictive of poor patient outcomes and thus may lead to the appropriate selection of adjuvant therapies at earlier UCC stages, which could improve patient prognosis. IntroductionUrothelial cell carcinoma (UCC) is one of the most common types of cancer in the USA, accounting for ~4.5% of all newly diagnosed cancer cases and 2.8% of all cancer-associated mortalities in 2013 (1). In the USA, the most common site of UCC is the bladder, and bladder UCC is the fourth most common type of cancer and the sixth leading cause of cancer-associated mortality in males (1). Bladder UCC may be classified into two subtypes at diagnosis, non-muscle and muscle-invasive, which exhibit distinct clinical features (2). The non-muscle-invasive subtype commonly recurs in the bladder cavity and accounts for 70-80% of cases of bladder UCC, with muscle invasion present in only 10-20% of cases. The 5-year survival rate of the non-muscle-invasive subtype of UCC is >90%. By contrast, muscle-invasive bladder UCC, which accounts for ~20% of bladder UCC cases, exhibits a poor prognosis with a 5-year survival rate of <50%. Carcinoma in situ (CIS), which is classified into the non-muscle invasive aggressive subtype, is localized to the epithelium and exhibits invasive and metastatic potential. In patients with aggressive bladder UCC (...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy

et al. 2016

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“…In addition, we confirmed CD8 + T cell localization using anti-CD8 antibody and tumor cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling assays in the tumor tissue by immunohistochemical staining analysis, as described previously using formalin-fixed, paraffin-embedded EG.7 and TC-1 tumor tissue specimens. 29 The analysis was recorded in five random fields for each slide and was performed by two investigators in a blinded fashion.…”

Section: Antitumor Efficacy Of Dcs Treated With Plga-npsmentioning

confidence: 99%

Toll-like receptor 3-induced immune response by poly(D,L-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy

Han¹,

Byeon²,

Kang³

et al. 2016

IJN

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“…En fonction du type de cancer considéré, l'impact du système du complément peut en effet varier en ce qui concerne les protéines impliquées, mais également en termes de valeur pronostique. Dans la majorité des cancers, comme le cancer du rein [14], du sein [12], du poumon [11], de l'ovaire [18] et urothéliales [15], les protéines du complément favorisent la croissance tumorale. Dans d'autres, comme le cancer de la prostate [19], ces protéines n'ont aucune influence sur la croissance tumorale, elles peuvent même la ralentir.…”

Section: Protéines Du Complément Et Contexte Tumoralunclassified