Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth in a spontaneous murine model of melanoma.

Abstract : Surgical resection of tumors is often followed by regrowth at the primary site and metastases may emerge rapidly following removal of the primary tumor. Macrophages are important drivers of tumor growth, and here we investigated their involvement in postoperative relapse as well as explore macrophage depletion as an adjuvant to surgical resection. RETAAD mice develop spontaneous metastatic melanoma that begins in the eye. Removal of the eyes as early as 1 week of age did not prevent the development of metastases; rather, surgery led to increased proliferation of tumor cells locally and in distant metastases. Surgery-induced increase in tumor cell proliferation correlated with increased macrophage density within the tumor. Moreover, macrophages stimulate tumor sphere formation from tumor cells of post-surgical but not control mice. Macrophage depletion with a diet containing the CSF-1R specific kinase inhibitor Ki20227 following surgery significantly reduced postoperative tumor recurrence and abrogated enhanced metastatic outgrowth. Our results confirm that tumor cells disseminate early, and show that macrophages contribute both to post-surgical tumor relapse and growth of metastases, likely through stimulating a population of tumor-initiating cells. Thus macrophage depletion warrants exploration as an adjuvant to surgical resection.
Type de document :
Article dans une revue
Oncotarget, Impact journals, 2015, 8 (6), pp.22857-68
Liste complète des métadonnées

Littérature citée [31 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01205344
Contributeur : Mireille Bos <>
Soumis le : vendredi 25 septembre 2015 - 13:28:47
Dernière modification le : jeudi 11 janvier 2018 - 06:19:05
Document(s) archivé(s) le : mardi 29 décembre 2015 - 10:02:11

Fichier

3127-42468-3-PB.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

  • HAL Id : inserm-01205344, version 1
  • PUBMED : 25762633

Collections

Citation

Muly Tham, Karen Khoo, Kim Pin Yeo, Masashi Kato, Amelle Prevost-Blondel, et al.. Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth in a spontaneous murine model of melanoma.. Oncotarget, Impact journals, 2015, 8 (6), pp.22857-68. 〈inserm-01205344〉

Partager

Métriques

Consultations de la notice

56

Téléchargements de fichiers

44