Adler, Omer and Zait, Yael and Cohen, Noam and Blazquez, Raquel and Doron, Hila and Monteran, Lea and Scharff, Yeela and Shami, Tamar and Mundhe, Dhanashree and Glehr, Gunther and Kanner, Andrew A. and Horn, Suzana and Yahalom, Vered and Haferkamp, Sebastian and Hutchinson, James A. and Bleckmann, Annalen and Nahary, Limor and Benhar, Itai and Katz, Shlomit Yust and Pukrop, Tobias and Erez, Neta (2023) Reciprocal interactions between innate immune cells and astrocytes facilitate neuroinflammation and brain metastasis via lipocalin-2. NATURE CANCER, 4 (3). 401-+. ISSN , 2662-1347
Full text not available from this repository. (Request a copy)Abstract
Adler et al. identify granulocyte-derived lipocalin-2 as a mediator of inflammatory astrocyte activation, which in turn facilitates brain metastasis in breast cancer and melanoma. Brain metastasis still encompass very grim prognosis and therefore understanding the underlying mechanisms is an urgent need toward developing better therapeutic strategies. We uncover the intricate interactions between recruited innate immune cells and resident astrocytes in the brain metastatic niche that facilitate metastasis of melanoma and breast cancer. We show that granulocyte-derived lipocalin-2 (LCN2) induces inflammatory activation of astrocytes, leading to myeloid cell recruitment to the brain. LCN2 is central to inducing neuroinflammation as its genetic targeting or bone-marrow transplantation from LCN2(-/-) mice was sufficient to attenuate neuroinflammation and inhibit brain metastasis. Moreover, high LCN2 levels in patient blood and brain metastases in multiple cancer types were strongly associated with disease progression and poor survival. Our findings uncover a previously unknown mechanism, establishing a central role for the reciprocal interactions between granulocytes and astrocytes in promoting brain metastasis and implicate LCN2 as a prognostic marker and potential therapeutic target.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GELATINASE-ASSOCIATED LIPOCALIN; MICROENVIRONMENTAL LANDSCAPE; INFLAMMATORY ACTIVATION; CANCER; ANGIOGENESIS; RECEPTOR; COMPLEX; PLAYS; IRON; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Mar 2024 11:46 |
| Last Modified: | 14 Mar 2024 11:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60096 |
Actions (login required)
 |
View Item |
