E-viri
Recenzirano
Odprti dostop
-
Parida, Pravat Kumar; Marquez-Palencia, Mauricio; Nair, Vidhya; Kaushik, Akash K.; Kim, Kangsan; Sudderth, Jessica; Quesada-Diaz, Eduardo; Cajigas, Ambar; Vemireddy, Vamsidhara; Gonzalez-Ericsson, Paula I.; Sanders, Melinda E.; Mobley, Bret C.; Huffman, Kenneth; Sahoo, Sunati; Alluri, Prasanna; Lewis, Cheryl; Peng, Yan; Bachoo, Robert M.; Arteaga, Carlos L.; Hanker, Ariella B.; DeBerardinis, Ralph J.; Malladi, Srinivas
Cell metabolism, 01/2022, Letnik: 34, Številka: 1Journal Article
HER2+ breast cancer patients are presented with either synchronous (S-BM), latent (Lat), or metachronous (M-BM) brain metastases. However, the basis for disparate metastatic fitness among disseminated tumor cells of similar oncotype within a distal organ remains unknown. Here, employing brain metastatic models, we show that metabolic diversity and plasticity within brain-tropic cells determine metastatic fitness. Lactate secreted by aggressive metastatic cells or lactate supplementation to mice bearing Lat cells limits innate immunosurveillance and triggers overt metastasis. Attenuating lactate metabolism in S-BM impedes metastasis, while M-BM adapt and survive as residual disease. In contrast to S-BM, Lat and M-BM survive in equilibrium with innate immunosurveillance, oxidize glutamine, and maintain cellular redox homeostasis through the anionic amino acid transporter xCT. Moreover, xCT expression is significantly higher in matched M-BM brain metastatic samples compared to primary tumors from HER2+ breast cancer patients. Inhibiting xCT function attenuates residual disease and recurrence in these preclinical models. Display omitted •Metabolically distinct HER2+ brain-tropic cells determine metastatic fitness•Tumor cell-secreted lactate modulates NK cell cytotoxicity•xCT-mediated cellular redox homeostasis promotes metastatic latency and relapse•Limiting xCT function attenuates metastatic latency and late recurrences The basis for disparate metastatic fitness among disseminated tumor cells of similar oncotype within a distal organ is unknown and vital to understand for better clinical management. Here, Parida et al. develop models of synchronous, latent residual, and metachronous brain metastatic disease and reveal distinct metabolic states associated with HER2+ breast cancer brain-tropic cells. Metabolic diversity and plasticity dictate cellular ability to survive and initiate metastasis.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.