Imaging Primary Prostate Cancer and Bone Metastasis

Effects of ALK1Fc treatment on prostate cancer cells interacting with bone and bone cells in bone metastasis models.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16576 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16576-e16576

Author(s):

Marianna Kruithof-de Julio ◽

Letizia Astrologo ◽

Eugenio Zoni ◽

Sofia Karkampouna ◽

Peter C Gray ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Cancer Cells ◽

Bone Cells ◽

Critical Role ◽

Prostate Cancer Cells ◽

Primary Prostate Cancer ◽

The Impact

e16576 Background: Prostate cancer is the second most common cancer in men worldwide. Lethality is normally associated with the consequences of metastasis rather than the primary tumor. In particular, bone is the most frequent site of metastasis and once prostate tumor cells are engrafted in the skeleton, curative therapy is no longer possible. Bone morphogenetic proteins (BMPs) play a critical role in bone physiology and pathology. However, little is known about the role of BMP9 and its signaling receptors, ALK1 and ALK2, in prostate cancer and bone metastasis. In this context, we investigate the impact of BMP9 on primary prostate cancer and derived bone metastasis. Methods: The human ALK1 extracellular domain (ECD) binds BMP9 and BMP10 with high affinity. In order to study the effect of BMP9 in vitro and in vivo we use a soluble chimeric protein, consisting of ALK1 ECD fused to human Fc (ALK1Fc), for preventing the activation of endogenous signaling. ALK1Fc sequesters BMP9 and BMP10, preserving the activation of ALK1 through other ligands. Results: We show that ALK1Fc reduces BMP9-mediated signaling and decreases proliferation of highly metastatic and tumor initiating human prostate cancer cells in vitro. In line with these observations, we demonstrate that ALK1Fc reduces tumor growth in vivo in an orthotopic transplantation model. The propensity of the primary prostate cancer to metastasize to the bone is also investigated. In particular, we report how the ALK1Fc influences the prostate cancer cells in vitro and in vivo when these are probed in different bone settings (co-culture with bone cells and intraosseous transplantation in mice). Conclusions: Our study provides the first demonstration that ALK1Fc inhibits prostate cancer cells growth identifying BMP9 as a putative therapeutic target and ALK1Fc as a potential therapy. All together, these findings justify the ongoing clinical development of drugs blocking ALK1 and ALK2 receptor activity.

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iRGD‐Liposomes Enhance Tumor Delivery and Therapeutic Efficacy of Antisense Oligonucleotide Drugs against Primary Prostate Cancer and Bone Metastasis

Advanced Functional Materials ◽

10.1002/adfm.202100478 ◽

2021 ◽

pp. 2100478

Author(s):

Jibin Guan ◽

Hong Guo ◽

Tang Tang ◽

Yihan Wang ◽

Yushuang Wei ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Antisense Oligonucleotide ◽

Therapeutic Efficacy ◽

Primary Prostate Cancer ◽

Tumor Delivery

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Two Cases of Synchronous Double Primary Prostate Cancer Accompanying Bone Metastasis and Colon Cancer

Journal of UOEH ◽

10.7888/juoeh.43.103 ◽

2021 ◽

Vol 43 (1) ◽

pp. 103-115

Author(s):

Atsushi TOYOFUKU ◽

Yugo IHA ◽

Yuki KOREEDA ◽

Kohei YOSHIDA ◽

Aiichiro HIGURE ◽

...

Keyword(s):

Prostate Cancer ◽

Colon Cancer ◽

Bone Metastasis ◽

Primary Prostate Cancer

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Protease-activated receptor-1 is upregulated in reactive stroma of primary prostate cancer and bone metastasis

The Prostate ◽

10.1002/pros.20920 ◽

2009 ◽

Vol 69 (7) ◽

pp. 727-736 ◽

Cited By ~ 15

Author(s):

Xiaotun Zhang ◽

Wenbin Wang ◽

Lawrence D. True ◽

Robert L. Vessella ◽

Thomas K. Takayama

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Reactive Stroma ◽

Primary Prostate Cancer ◽

Protease Activated Receptor 1

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

Journal of Experimental Medicine ◽

10.1084/jem.20190158 ◽

2019 ◽

Vol 216 (12) ◽

pp. 2883-2899 ◽

Cited By ~ 25

Author(s):

Jinlu Dai ◽

June Escara-Wilke ◽

Jill M. Keller ◽

Younghun Jung ◽

Russell S. Taichman ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Bone Metastasis ◽

Pyruvate Kinase ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Pyruvate Kinase M2 ◽

Premetastatic Niche ◽

Primary Prostate Cancer ◽

Niche Formation

Prostate cancer (PCa) metastasizes selectively to bone through unknown mechanisms. In the current study, we identified exosome-mediated transfer of pyruvate kinase M2 (PKM2) from PCa cells into bone marrow stromal cells (BMSCs) as a novel mechanism through which primary tumor-derived exosomes promote premetastatic niche formation. We found that PKM2 up-regulates BMSC CXCL12 production in a HIF-1α-dependent fashion, which subsequently enhances PCa seeding and growth in the bone marrow. Furthermore, serum-derived exosomes from patients with either primary PCa or PCa metastasis, as opposed to healthy men, reveal that increased exosome PKM2 expression is associated with metastasis, suggesting clinical relevance of exosome PKM2 in PCa. Targeting the exosome-induced CXCL12 axis diminished exosome-mediated bone metastasis. In summary, primary PCa cells educate the bone marrow to create a premetastatic niche through primary PCa exosome-mediated transfer of PKM2 into BMSCs and subsequent up-regulation of CXCL12. This novel mechanism indicates the potential for exosome PKM2 as a biomarker and suggests therapeutic targets for PCa bone metastasis.

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