Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform

Liotti, Antonietta; Civita, Evelina La; Cennamo, Michele; Crocetto, Felice; Ferro, Matteo; Guadagno, Elia; Insabato, Luigi; Imbimbo, Ciro; Palmieri, Alessandro; Mirone, Vincenzo; Liguoro, Pasquale; Formisano, Pietro; Béguinot, Francesco; Terracciano, Daniela

doi:10.1002/pros.24117

Cited by 41 publications

(26 citation statements)

References 51 publications

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“…In addition to KMT2B , we also found several other gene candidates on HBV‐related GC for further studies. TUBB2B and FGF12 have been suggested to play vital functions in prostate cancer ( Liotti et al., 2021 ), neuroblastoma ( Zafar et al., 2021 ), and esophageal squamous cell carcinoma ( Bhushan et al., 2017 ); however, their roles in HBV-related GC development have never been documented and merit further investigations.…”

Section: Discussionmentioning

confidence: 99%

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer

Luo

et al. 2022

Front. Cell. Infect. Microbiol.

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Hepatitis B virus (HBV) infection has been reported to be associated with gastric cancer (GC). Nonetheless, no study has revealed the role of HBV infection in the survival of patients with GC, and the mutation profiles of HBV-infected patients with GC have never been documented. Here, we performed an updated meta-analysis and found a significantly increased risk of GC in HBV-infected individuals (sOR, 1.29; 95% CI, 1.22-1.37). Furthermore, we observed that in the Anhui area, the rate of serum HBsAg positivity (OR, 1.62; 95% CI, 1.03-2.55) was significantly higher in GC patients than in controls. Moreover, our results showed that HBV-positive patients had significantly worse disease-free survival (HR, 1.98; 95% CI, 1.39-2.82) and overall survival (HR, 1.84; 95% CI, 1.19-2.85) than HBV-negative patients. The results of Cox proportional hazards regression proved that HBV infection was an independent adverse prognostic factor in GC. Furthermore, by performing targeted-NGS, we found unique mutation profiles in HBV-infected GC samples, including five frequently mutated protein-coding genes (KMT2B, KMT2D, SOX1, FGF12, and TUBB2B). Expression and survival analyses of these genes identified three novel candidate genes that may have potential roles in GC development. Gene Ontology enrichment analysis showed that the recurrent mutations in HBV-positive GC samples were related to cell proliferation, cell migration, and transcription. Taking together, our study proved that HBV infection is an independent prognostic factor in GC patients. The unique mutation profiles of HBV-infected patients with GC open a new research direction toward the underling mechanism between HBV infection and GC.

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Section: Discussionmentioning

confidence: 99%

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer

Luo

et al. 2022

Front. Cell. Infect. Microbiol.

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“…To address this issue, it could be informative to investigate the effect of PPAT-released factors on the PCa cell aggressive phenotype. We previously demonstrated that adipose tissue-released IGF-1 contributed to docetaxel resistance of PCa cells [ 15 ]. In addition, the ability of adipocyte secretome to promote metastatic expansion has been clearly demonstrated in breast cancer [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…For Western blot assays, cells were washed with ice-cold phosphate-buffered saline (PBS) and harvested in a Laemmli buffer (with β-mercaptoethanol) containing a mixture of phosphatase inhibitors (0.5 mM sodium vanadate, 2 mM sodium pyrophosphate, 5 mM β-glycerolphosphate, and 50 mM sodium fluoride) and the protease inhibitor phenylmethylsulfonyl fluoride (Sigma–Aldrich). Western blots were carried out as previously reported [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…This fat layer is contiguous to the gland capsule [ 12 ], making it plausible that PPAT affects the prostate cancer malignant phenotype [ 13 , 14 ]. Accordingly, we recently demonstrated that a paracrine secretion of IGF-1 by PPAT reduced the docetaxel response of androgen-independent (AI) PCa cell lines [ 15 ]. Ribeiro et al [ 14 ] showed that PPAT collected from obese patients was able to enhance migration of androgen-dependent (AD) and castration-resistant PCa cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor

et al. 2021

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Periprostatic adipose tissue (PPAT) has emerged as a key player in the prostate cancer (PCa) microenvironment. In this study, we evaluated the ability of PPAT to promote PCa cell migration, as well as the molecular mechanisms involved. Methods: We collected conditioned mediums from in vitro differentiated adipocytes isolated from PPAT taken from PCa patients during radical prostatectomy. Migration was studied by scratch assay. Results: Culture with CM of human PPAT (AdipoCM) promotes migration in two different human androgen-independent (AI) PCa cell lines (DU145 and PC3) and upregulated the expression of CTGF. SB431542, a well-known TGFβ receptor inhibitor, counteracts the increased migration observed in presence of AdipoCM and decreased CTGF expression, suggesting that a paracrine secretion of TGFβ by PPAT affects motility of PCa cells. Conclusions: Collectively, our study showed that factors secreted by PPAT enhanced migration through CTGF upregulation in AI PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and TGFβ/CTGF axis to fight advanced PCa dissemination.

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“…Nevertheless, an under-studied AT that is particularly pertinent to the etiology of PCa is the periprostatic adipose tissue (PPAT) that is situated in the proximity of the prostate [ 17 ]. Indeed, PPAT dysfunction and inflammation not only amplify rudimentary neoplastic alterations of the healthy prostate, but also promote PCa progression, metastasis, and resistance to chemotherapy [ 17 , 18 , 19 , 20 , 21 , 22 ]. Compared to other adipose depots, the cellular and molecular heterogeneity as well as the thermogenic potential of PPAT remain largely uninvestigated.…”

Section: Introductionmentioning

confidence: 99%

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue

AlZaim

Al-Saidi

Hammoud

et al. 2022

Cancers

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The increased global prevalence of metabolic disorders including obesity, insulin resistance, metabolic syndrome and diabetes is mirrored by an increased incidence of prostate cancer (PCa). Ample evidence suggests that these metabolic disorders, being characterized by adipose tissue (AT) expansion and inflammation, not only present as risk factors for the development of PCa, but also drive its increased aggressiveness, enhanced progression, and metastasis. Despite the emerging molecular mechanisms linking AT dysfunction to the various hallmarks of PCa, thromboinflammatory processes implicated in the crosstalk between these diseases have not been thoroughly investigated. This is of particular importance as both diseases present states of hypercoagulability. Accumulating evidence implicates tissue factor, thrombin, and active factor X as well as other players of the coagulation cascade in the pathophysiological processes driving cancer development and progression. In this regard, it becomes pivotal to elucidate the thromboinflammatory processes occurring in the periprostatic adipose tissue (PPAT), a fundamental microenvironmental niche of the prostate. Here, we highlight key findings linking thromboinflammation and the pleiotropic effects of coagulation factors and their inhibitors in metabolic diseases, PCa, and their crosstalk. We also propose several novel therapeutic targets and therapeutic interventions possibly modulating the interaction between these pathological states.

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Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform

Cited by 41 publications

References 51 publications

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer

Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue

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