Ksiazkiewicz, Magdalena and Gottfried, Eva and Kreutz, Marina and Mack, Matthias and Hofstaedter, Ferdinand and Kunz-Schughart, Leoni A. (2010) Importance of CCL2-CCR2A/2B signaling for monocyte migration into spheroids of breast cancer-derived fibroblasts. IMMUNOBIOLOGY, 215 (9-10). pp. 737-747. ISSN 0171-2985,
Full text not available from this repository. (Request a copy)Abstract
A considerable fraction of tumor-associated macrophages (TAM) is located in the fibroblast-rich stromal compartment of desmoplastic breast carcinoma. We analyzed the migratory activity of blood monocytes (MO), the precursor cells of TAM, into 3-D cultures of carcinoma cells and fibroblasts from breast tumor origin. MO migration into breast tumor spheroids was highly variable: Hs578T spheroids showed high MO infiltration rates, T47D cultures were intermediate, whereas BT549, BT474 and MCF-7 spheroids were poorly infiltrated. MO infiltration was also high in tumor-derived fibroblast spheroids; however, no MO subpopulation with specific infiltrative potential was identified by CD14/CD16 expression profile. The infiltration of MO could be inhibited by pre-exposure to pertussis and cholera toxins, but only pertussis toxin, which blocks G(i) protein function, entirely inhibited MO migration. The G(i) coupled CCL2 receptor CCR2A/2B was expressed on roughly all MO. Furthermore, highly infiltrated tumor-derived fibroblast and Hs578T spheroids secreted considerable amounts of CCL2. In line with this, the infiltration of MO into fibroblast spheroids was suppressed by either addition of recombinant CCL2 to disturb the CCL2 gradient or by pre-incubation of MO with a CCR2A/2B blocking antibody. MO infiltration of Hs578T spheroids, however, could not be inhibited by CCL2 receptor blockade. Our study clearly shows that the CCL2-CCR2A/2B pathway is crucial for the recruitment of blood MO into tumor fibroblastic areas, whereas additional factors may be relevant for the migration of MO into tumor cell sites. (C) 2010 Elsevier GmbH. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-ASSOCIATED MACROPHAGES; CHEMOATTRACTANT PROTEIN-1 EXPRESSION; HUMAN DERMAL FIBROBLASTS; TRANSENDOTHELIAL MIGRATION; BLOOD MONOCYTES; MAMMARY-TUMORS; IN-VIVO; INFILTRATION; PROGRESSION; CELLS; Breast cancer; CCR2A/2B; MCP-1/CCL2; Migration; Monocytes; Multicellular spheroid; Spheroid co-culture; Tumor-associated fibroblast |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Innere Medizin II Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2020 05:21 |
| Last Modified: | 15 Jul 2020 05:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24237 |
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