The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence

Schörghofer, David; Kinslechner, Katharina; Preitschopf, Andrea; Schütz, Birgit; Röhrl, Clemens; Hengstschläger, Markus; Stangl, Herbert; Mikula, Mario

doi:10.1186/s12958-015-0087-z

Cited by 67 publications

(75 citation statements)

References 39 publications

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“…High SR-B1 expression has been demonstrated in diverse cancer cell lines and patient tumor samples [79][80][81] and correlates with worse patient survival [82]. SR-B1 can promote tumor progression through three different mechanisms.…”

Section: Sr-b1 Promotes Cancer Progression: Sr-b1 Antagonist As Anti-mentioning

confidence: 99%

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

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Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach. Keywords:Cancer immunotherapy r CD5 r Danger signal r Immune-checkpoint r Scavenger receptor r Scavenger receptor class B type 1 r Toll-like receptors IntroductionThe cancer-immunity cycle can be subverted by tumors at many steps, thus novel therapeutic interventions should be considered for all these possibilities [1]. This cycle starts with the release of tumor antigens and their subsequent capture by professional antigen-presenting cells (mainly, dendritic cells; DCs) for the activation of effector cells of the innate and adaptive immune Correspondence: Dr. Pedro Berraondo e-mail: pberraondol@unav.es system. This is a highly regulated process aimed at maintaining the integrity of the host without inducing significant side effects (e.g., inflammation or autoimmunity) [2]. Tissue homeostasis involves phagocytic processes to remove the excess of native or modified molecules from unviable or stressed cells, as well as from invading microbial agents [3]. Such molecules include lipids, whose intracellular levels should be carefully controlled to sustain proper cell metabolism; endogenous glyco-and lipo-proteins, damaged or * These authors contributed equally to this work. * * These authors are senior co-authors of this work. [4,5]. This phagocytic activity should be coupled to an alarm signal system that awakens other effector mechanisms of the immune system when the tissue damage cannot be controlled by the removal of the endogenous or exogenous molecules. To this end, the immune system has a myriad of specialized soluble or membrane-bound receptors called pattern recognition receptors (PRRs). These PRRs are non-polymorphic, nonclonally distributed, and germ-line encoded receptors recognizing microorganism-associated molecular patterns (MAMPs) -tha...

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Section: Sr-b1 Promotes Cancer Progression: Sr-b1 Antagonist As Anti-mentioning

confidence: 99%

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

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“…Twiddy et al (36) found that SR-BI downregulation caused a significant reduction in prostate-specific antigen production and decreased the viability of prostate cancer cell lines in vitro. Previous studies revealed that SR-BI was associated with more aggressive cancer phenotypes and could serve a tumor-promoting function in breast and prostate cancer (35,37). However, in gastric adenocarcinoma, the role of SR-BI appeared to be different.…”

Section: Sr-bi Expression % (N) -----------------------------------mentioning

confidence: 96%

“…The results of a previous study revealed that high SR-BI expression was an independent factor predictive of poor prognosis for patients with breast cancer (35). Schörghofer et al (37) reported that high SR-BI expression was associated with shorter disease-free survival times in prostate cancer. On the contrary, in gastric adenocarcinoma, patients with low SR-BI expression had significantly poorer prognosis than patients with high SR-BI expression, indicating that different mechanisms were involved.…”

Section: Sr-bi Expression % (N) -----------------------------------mentioning

confidence: 98%

Low scavenger receptor classï¿½B typeï¿½I expression is associated with gastric adenocarcinoma tumor aggressiveness

Wang

Yuan

et al. 2018

Oncol Lett

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Abstract. Scavenger receptor class B type I (SR-BI), a well-documented high-density lipoprotein receptor, has been implicated in the development and progression of human cancer. However, little is known regarding the expression profile and clinical value of SR-BI in gastric adenocarcinoma. In the present study immunohistochemistry analysis was performed on a well-annotated gastric adenocarcinoma tissue microarray to investigate the association between SR-BI expression and clinicopathological parameters or patient outcome. The results revealed that SR-BI expression was detected in 69% of the 84 gastric adenocarcinomas. Moreover, a significant association was observed between low SR-BI expression and poor histological grade, higher Tumor-Node-Metastasis T stage, higher N stage and diffuse type carcinoma. Low SR-BI expression was also significantly associated with a shorter overall survival time in patients with gastric adenocarcinoma, although it was not an independent prognostic factor. Overall, the results of the present study demonstrated that SR-BI was possibly involved in gastric carcinogenesis and could be used as a biomarker to predict malignancy of gastric adenocarcinoma.

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“…It is well-known that SR-B1 is of vital importance in high-density lipoprotein (HDL)-cholesterol metabolism 6 and hepatitis C virus entry. [7][8][9] It has been reported that SR-B1 also plays a critical role in cancers including breast cancer, [10][11][12] prostate cancer, 13,14 and nasopharyngeal cancer. 15 The results showed that the expression of SR-B1 was highly up-regulated and SR-B1 functioned as an oncogene, promoting progression in these cancers.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, high SR-B1 expression was significantly associated with poor clinical outcome in breast cancer 12 and prostate cancer. 14 However, expression and clinical value of SR-B1 in ccRCC has not been well addressed so far.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma

Lou

et al. 2017

Tumour Biol.

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Aberrant expression of scavenger receptor class B type 1 has been reported in several human cancers. Nevertheless, the roles of scavenger receptor class B type 1 in clear cell renal cell carcinoma remain unclear. The aim of this study was to evaluate the diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma. The messenger RNA level of scavenger receptor class B type 1 in clear cell renal cell carcinoma tissues was detected by quantitative reverse transcription polymerase chain reaction, while protein level was determined by western blot and immunohistochemistry. The lipid content between clear cell renal cell carcinoma tissues and normal kidney tissues was differentiated by Oil Red O and hematoxylin-eosin staining. The diagnostic value of scavenger receptor class B type 1 was determined by receiver operating characteristic curve. The prognostic significance of scavenger receptor class B type 1 was assessed by Kaplan-Meier analysis and Cox regression analysis. Our results showed that the expression of scavenger receptor class B type 1 in clear cell renal cell carcinoma tissues at both messenger RNA and protein level was much higher than that in normal kidney tissues. Receiver operating characteristic curve analysis exhibited a significant value of area under the curve (0.8486, 95% confidence interval: 0.7926-0.9045) with strong sensitivity (0.75, 95% confidence interval: 0.6535-0.8312) and specificity (0.90, 95% confidence interval: 0.8238-0.9510). Kaplan-Meier analysis revealed that patients with higher scavenger receptor class B type 1 expression had shorter progression-free survival time. Cox analysis indicated that scavenger receptor class B type 1 was an independent prognostic biomarker. In conclusion, our findings implied that scavenger receptor class B type 1 might serve as a diagnostic and independent prognostic biomarker in clear cell renal cell carcinoma.

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The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence

Cited by 67 publications

References 39 publications

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

Low scavenger receptor classï¿½B typeï¿½I expression is associated with gastric adenocarcinoma tumor aggressiveness

Diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma

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