Tumor-derived OBP2A promotes prostate cancer castration resistance
© 2022 Jeong et al..
Androgen deprivation therapy (ADT) is a systemic therapy for advanced prostate cancer (PCa); although most patients initially respond to ADT, almost all cancers eventually develop castration-resistant PCa (CRPC). Currently, most research focuses on castration-resistant tumors, and the role of tumors in remission is almost completely ignored. Here, we report that odorant-binding protein (OBP2A) released from tumors in remission during ADT catches survival factors, such as CXCL15/IL8, to promote PCa cell androgen-independent growth and enhance the infiltration of myeloid-derived suppressor cells (MDSCs) into tumor microenvironment, leading to the emergence of castration resistance. OBP2A knockdown significantly inhibits CRPC and metastatic CRPC development and improves therapeutic efficacy of CTLA-4/PD-1 antibodies. Treatment with OBP2A-binding ligand α-pinene interrupts the function of OBP2A and suppresses CRPC development. Furthermore, α-pinene-conjugated doxorubicin/docetaxel can be specifically delivered to tumors, resulting in improved anticancer efficacy. Thus, our studies establish a novel concept for the emergence of PCa castration resistance and provide new therapeutic strategies for advanced PCa.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:220 |
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| Enthalten in: |
The Journal of experimental medicine - 220(2023), 3 vom: 06. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jeong, Ji-Hak [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.01.2023 Date Revised 01.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1084/jem.20211546 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350592128 |
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| 041 | |a eng | ||
| 100 | 1 | |a Jeong, Ji-Hak |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tumor-derived OBP2A promotes prostate cancer castration resistance |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 12.01.2023 | ||
| 500 | |a Date Revised 01.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 Jeong et al. | ||
| 520 | |a Androgen deprivation therapy (ADT) is a systemic therapy for advanced prostate cancer (PCa); although most patients initially respond to ADT, almost all cancers eventually develop castration-resistant PCa (CRPC). Currently, most research focuses on castration-resistant tumors, and the role of tumors in remission is almost completely ignored. Here, we report that odorant-binding protein (OBP2A) released from tumors in remission during ADT catches survival factors, such as CXCL15/IL8, to promote PCa cell androgen-independent growth and enhance the infiltration of myeloid-derived suppressor cells (MDSCs) into tumor microenvironment, leading to the emergence of castration resistance. OBP2A knockdown significantly inhibits CRPC and metastatic CRPC development and improves therapeutic efficacy of CTLA-4/PD-1 antibodies. Treatment with OBP2A-binding ligand α-pinene interrupts the function of OBP2A and suppresses CRPC development. Furthermore, α-pinene-conjugated doxorubicin/docetaxel can be specifically delivered to tumors, resulting in improved anticancer efficacy. Thus, our studies establish a novel concept for the emergence of PCa castration resistance and provide new therapeutic strategies for advanced PCa | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a alpha-pinene |2 NLM | |
| 650 | 7 | |a JPF3YI7O34 |2 NLM | |
| 650 | 7 | |a Androgen Antagonists |2 NLM | |
| 650 | 7 | |a Androgens |2 NLM | |
| 650 | 7 | |a Receptors, Androgen |2 NLM | |
| 650 | 7 | |a Bicyclic Monoterpenes |2 NLM | |
| 650 | 7 | |a OBP2A protein, human |2 NLM | |
| 650 | 7 | |a Lipocalins |2 NLM | |
| 650 | 7 | |a Antibodies |2 NLM | |
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| 700 | 1 | |a Zhong, Shangwei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fuzhuo |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Changhao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xueyan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qingqing |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Shoujiao |e verfasserin |4 aut | |
| 700 | 1 | |a Park, HaJeung |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, You Mie |e verfasserin |4 aut | |
| 700 | 1 | |a Dhillon, Jasreman |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Jun-Li |e verfasserin |4 aut | |
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