ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression
Small extracellular vesicles (SEVs) are functional messengers of certain cellular niches that permit noncontact cell communications. Whether niche-specific SEVs fulfill this role in cancer is unclear. Here, we used 7 cell type-specific mouse Cre lines to conditionally knock out Vps33b in Cdh5+ or Tie2+ endothelial cells (ECs), Lepr+ BM perivascular cells, Osx+ osteoprogenitor cells, Pf4+ megakaryocytes, and Tcf21+ spleen stromal cells. We then examined the effects of reduced SEV secretion on progression of MLL-AF9-induced acute myeloid leukemia (AML), as well as normal hematopoiesis. Blocking SEV secretion from ECs, but not perivascular cells, megakaryocytes, or spleen stromal cells, markedly delayed the leukemia progression. Notably, reducing SEV production from ECs had no effect on normal hematopoiesis. Protein analysis showed that EC-derived SEVs contained a high level of ANGPTL2, which accelerated leukemia progression via binding to the LILRB2 receptor. Moreover, ANGPTL2-SEVs released from ECs were governed by VPS33B. Importantly, ANGPTL2-SEVs were also required for primary human AML cell maintenance. These findings demonstrate a role of niche-specific SEVs in cancer development and suggest targeting of ANGPTL2-SEVs from ECs as a potential strategy to interfere with certain types of AML.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
|---|---|
| Enthalten in: |
The Journal of clinical investigation - 131(2021), 1 vom: 04. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Huang, Dan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Angiopoietin-Like Protein 2 |
|---|
| Anmerkungen: |
Date Completed 07.09.2021 Date Revised 04.12.2021 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1172/JCI138986 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM316770469 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM316770469 | ||
| 003 | DE-627 | ||
| 005 | 20231225161810.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/JCI138986 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1055.xml |
| 035 | |a (DE-627)NLM316770469 | ||
| 035 | |a (NLM)33108353 | ||
| 035 | |a (PII)138986 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Huang, Dan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.09.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Small extracellular vesicles (SEVs) are functional messengers of certain cellular niches that permit noncontact cell communications. Whether niche-specific SEVs fulfill this role in cancer is unclear. Here, we used 7 cell type-specific mouse Cre lines to conditionally knock out Vps33b in Cdh5+ or Tie2+ endothelial cells (ECs), Lepr+ BM perivascular cells, Osx+ osteoprogenitor cells, Pf4+ megakaryocytes, and Tcf21+ spleen stromal cells. We then examined the effects of reduced SEV secretion on progression of MLL-AF9-induced acute myeloid leukemia (AML), as well as normal hematopoiesis. Blocking SEV secretion from ECs, but not perivascular cells, megakaryocytes, or spleen stromal cells, markedly delayed the leukemia progression. Notably, reducing SEV production from ECs had no effect on normal hematopoiesis. Protein analysis showed that EC-derived SEVs contained a high level of ANGPTL2, which accelerated leukemia progression via binding to the LILRB2 receptor. Moreover, ANGPTL2-SEVs released from ECs were governed by VPS33B. Importantly, ANGPTL2-SEVs were also required for primary human AML cell maintenance. These findings demonstrate a role of niche-specific SEVs in cancer development and suggest targeting of ANGPTL2-SEVs from ECs as a potential strategy to interfere with certain types of AML | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Hematology | |
| 650 | 4 | |a Leukemias | |
| 650 | 4 | |a Stem cells | |
| 650 | 7 | |a Angiopoietin-Like Protein 2 |2 NLM | |
| 650 | 7 | |a Angiopoietin-like Proteins |2 NLM | |
| 650 | 7 | |a Angptl2 protein, mouse |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 700 | 1 | |a Sun, Guohuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Xiaoxin |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xiaoxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Zhaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhuo |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Shihui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ligen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Bo O |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Junke |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Tao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of clinical investigation |d 1924 |g 131(2021), 1 vom: 04. Jan. |w (DE-627)NLM000005487 |x 1558-8238 |7 nnns |
| 773 | 1 | 8 | |g volume:131 |g year:2021 |g number:1 |g day:04 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/JCI138986 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 131 |j 2021 |e 1 |b 04 |c 01 | ||