Knockdown of scavenger receptor Class B Type I reduces prostate specific antigen secretion and viability of prostate cancer cells

Twiddy, Alexis L.; Cox, Michael; Wasan, Kishor M.

doi:10.1002/pros.21499

Cited by 46 publications

(63 citation statements)

References 63 publications

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“…SR-B1 has been implicated in several biological processes such as apoptosis [86,87] entry through TRPC3 channels, leading to dampened cytokine production in response to CpG via TLR9 activation [90]. Disrupting SR-B1 function by genetic or chemical inhibitors may decrease tumor cell malignancy [85,91]. The main mechanisms of action proposed for these therapeutic interventions are the reduced availability of cholesterol and the decreased activation of the PI3K/AKT pathway.…”

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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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confidence: 99%

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

et al. 2017

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“…Further study is therefore required to answer these questions. Several studies have reported the role of SR-BI in diverse solid tumors (7,35,36). For instance, SR-BI was shown to mediate the proliferative and anti-apoptotic features of HDL in MCF-7 breast cancer cells through modulation of cholesterol metabolism (7,8).…”

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

confidence: 99%

“…For instance, SR-BI was shown to mediate the proliferative and anti-apoptotic features of HDL in MCF-7 breast cancer cells through modulation of cholesterol metabolism (7,8). 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).…”

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

confidence: 99%

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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“…Second, spherical forms of HDL engage the SR-B1 receptor, 3 a receptor found in a variety of cell types, including tumor cells. 65, 66 This may confer inherent target specificity to a class of cells of tremendous interest for therapeutic targeting. Emerging evidence supports the notion that SR-B1 is critical for maintaining cholesterol homeostasis, and that adequate cholesterol uptake is critical for supporting tumor cell growth.…”

Section: Mimics Of Spherical Hdl For Drug Deliverymentioning

confidence: 99%

High-density lipoproteins for therapeutic delivery systems

2016

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High-density lipoproteins (HDL) are a class of natural nanostructures found in the blood and are composed of lipids, proteins, and nucleic acids (e.g. microRNA). Their size, which appears to be well-suited for both tissue penetration/retention as well as payload delivery, long circulation half-life, avoidance of endosomal sequestration, and potential low toxicity are all excellent properties to model in a drug delivery vehicle. In this review, we consider high-density lipoproteins for therapeutic delivery systems. First we discuss the structure and function of natural HDL, describing in detail its biogenesis and transformation from immature, discoidal forms, to more mature, spherical forms. Next we consider features of HDL making them suitable vehicles for drug delivery. We then describe the use of natural HDL, discoidal HDL analogs, and spherical HDL analogs to deliver various classes of drugs, including small molecules, lipids, and oligonucleotides. We briefly consider the notion that the drug delivery vehicles themselves are therapeutic, constituting entities that exhibit “theralivery.” Finally, we discuss challenges and future directions in the field.

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Knockdown of scavenger receptor Class B Type I reduces prostate specific antigen secretion and viability of prostate cancer cells

Cited by 46 publications

References 63 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

High-density lipoproteins for therapeutic delivery systems

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