Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis

Dai, Jinlu; Escara‐Wilke, June; Keller, Jill M.; Jung, Younghun; Taichman, Russell S.; Pienta, Kenneth J.; Keller, Evan T.

doi:10.1084/jem.20190158

Cited by 133 publications

(129 citation statements)

References 57 publications

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“…Furthermore, exosome size was measured using NTA, and the majority of vesicle particles were 50-150 nm in diameter. CD9 and CD63 are known exosomal protein markers routinely used for the determination of serum exosomes [25][26][27] . These results demonstrated that we have successfully extracted exosomes from serum.…”

Section: Discussionmentioning

confidence: 99%

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

Zhong¹,

Wang²,

Li³

et al. 2020

OTT

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Purpose: There is an urgent need for new biomarkers for the diagnosis of breast cancer. Exosomes can communicate with cells through transport molecules, including long-chain noncoding RNA (lncRNA), which is considered as a promising noninvasive biomarker. Here, we aimed to determine the potential of long noncoding RNA (lncRNA) H19 in the circulating exosomes for the diagnosis of breast cancer (BC). Materials and Methods: We measured the levels of lncRNA H19 in serum-derived exosomes from patients with breast cancer (BC) or benign breast disease (BBD) and healthy subjects, using quantitative real-time PCR. H19 levels were also measured for pre-operative and post-operative patients. Receiver operating characteristic curve was constructed, and the area under the curve (AUC) was calculated to determine the applicability of exosomal H19 levels as biomarkers in BC. The relationship between H19 relative expression and clinical features of BC patients was also analyzed. Results: Exosomal H19 expression levels were upregulated in patients with BC compared to that in patients with BBD and healthy controls (BC vs BBD, P < 0.001; BC vs healthy subjects, P < 0.001). The median serum exosomal H19 levels were significantly lower in post-operative than that in the pre-operative patients (P < 0.001). The AUC for exosomal H19 analysis was 0.870 (95% CI: 0.774-0.966) with a sensitivity of 87.0% and specificity of 70.6%, which was higher than the AUCs for CA15-3 and CEA, ie, 0.822 and 0.811, respectively. Moreover, exosomal H19 expression levels were associated with lymph node metastasis (P = 0.039), distant metastasis (P = 0.008), TNM stages (P = 0.022), ER (P=0.009), PR (P = 0.018), and Her-2 (P = 0.021). Conclusion: Our results indicated that serum exosomal H19 acts as a novel biomarker for the diagnosis of BC.

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Section: Discussionmentioning

confidence: 99%

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

Zhong¹,

Wang²,

Li³

et al. 2020

OTT

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“…Even if the biological mechanisms underlying this hypothesis are not yet known in detail, most of the evidences obtained in the literature confirm that the treatments for ablative purpose of the primitive tumor, aiming to reduce the local load of disease, are able to positively influence the biological behavior of secondary locations and their response to adjuvant therapies 40 , resulting in an overall improvement of the OS, as well as quality of life. With particular regard to the radiometabolic treatment with 223Ra, it is known that this acts directly on the microenvironment surrounding the bone metastases 41 ; in our opinion it is reasonable to think that the mentioned microenvironment is, in a complex way, favored by the presence of the primary site of disease and that consequently its ablation would be decisive for a better control of systemic disease 42 .…”

Section: Role Of Primary Tumor Cytoreduction In Mcrpcmentioning

confidence: 99%

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Frantellizzi

Costa

Mascia

et al. 2020

Clinical Genitourinary Cancer

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MicroabstractThis study investigates the impact on the overall survival of previous radical primary treatment in mCRPC patients treated with 223-Ra. In this multicenter retrospective study, we enrolled 275 consecutive patients. Results obtained showed a clear advantage for patients subjected to radical primary treatment in respect of those without, with an estimated median survival of 18 months and 11, respectively. AbstractBackground. We provide an analysis aiming to investigate, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy (RP) or external beam radiotherapy (EBRT)) in terms of overall survival, in mCRPC patients treated with 223-Ra. Materials and methodsIn this multicenter retrospective study we enrolled 275 consecutive patients. Demographics and clinical data, as well as mCRPC characteristics, have been obtained and evaluated at baseline and the end of the treatment or progression. 223-Ra has been administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: men previously treated with primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and patient with no prior primary treatment available (NO). Results128 out of 275 patients (46.5%) are alive and currently on follow-up; 103 patients (37.4%) dropped treatment out for disease progression or onset of comorbidities, and 147 patients died during the follow-up (53.5%). 93 patients underwent RP, 76 patients performed ablative EBRT. 132 patients enrolled in the RP/EBRT group (48%), 143 patients in the NO group (52%).Data showed a clear advantage for patients subjected to RP or EBRT in respect of those without primary treatment performed, with an estimated median survival of 18 months and 11 respectively (p<0.001). The multivariate analysis corroborated this trending results, returning in an HR of 0.7 (p-value= 0.0443), confirming the best outcome of the RP/EBRT group. 3 Conclusions Previous radical treatment plays a protective role in mCRPC patients who underwent 223-Ra treatment.

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“…CXCL12 and RANKL, cytokines that are overexpressed by osteoblast-lineage cells and circulate in the blood, can attract CXCR4 and RANK, which are highly expressed on mammary tumor cells, inducing the latter to migrate to the bone surface. A new study regarding prostate cancer bone metastasis demonstrated that prostate cancer cells that produce exosomes can transfer pyruvate kinase M2 (PKM2) into bone marrow stromal cells and up-regulate CXCL12 in these cells (Dai et al, 2019). A similar mechanism remains to be elucidated for breast cancer bone metastasis.…”

Section: Bone Cellsmentioning

confidence: 99%

RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies

Dang

et al. 2020

Front. Cell Dev. Biol.

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Breast cancer remains one of the most life-threatening tumors affecting women. Most patients with advanced breast cancer eventually develop metastatic diseases, which cause significant morbidity and mortality. Approximately two-thirds of patients with advanced breast cancer exhibit osteolytic-type bone metastasis, which seriously reduce the quality of life. Therefore, development of novel therapeutic strategies for treating breast cancer patients with bone metastasis is urgently required. The "seed and soil" theory, which describes the interaction between the circulating breast cancer cells (seeds) and bone microenvironment (soil), is widely accepted as the mechanism underlying metastasis. Disruption of any step in this cycle might have promising antimetastasis implications. The interaction of receptor activator of nuclear factor-κB ligand (RANKL) and its receptor RANK is fundamental in this vicious cycle and has been shown to be a novel effective therapeutic target. A series of therapeutic strategies have been developed to intervene in this cross-talk. Therefore, in this review, we have systematically introduced the functions of the RANKL/RANK signaling system in breast cancer and discussed related therapeutic strategies.

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Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis

Cited by 133 publications

References 57 publications

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies

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