TY - JOUR
T1 - Melanoma miRNA trafficking controls tumour primary niche formation
AU - Dror, Shani
AU - Sander, Laureen
AU - Schwartz, Hila
AU - Sheinboim, Danna
AU - Barzilai, Aviv
AU - Dishon, Yuval
AU - Apcher, Sebastien
AU - Golan, Tamar
AU - Greenberger, Shoshana
AU - Barshack, Iris
AU - Malcov, Hagar
AU - Zilberberg, Alona
AU - Levin, Lotan
AU - Nessling, Michelle
AU - Friedmann, Yael
AU - Igras, Vivien
AU - Barzilay, Ohad
AU - Vaknine, Hananya
AU - Brenner, Ronen
AU - Zinger, Assaf
AU - Schroeder, Avi
AU - Gonen, Pinchas
AU - Khaled, Mehdi
AU - Erez, Neta
AU - Hoheisel, Jörg D.
AU - Levy, Carmit
N1 - Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialized in releasing pigment vesicles, termed melanosomes. In melanoma in situ, we found melanosome markers in distal fibroblasts before melanoma invasion. The melanosomes carry microRNAs into primary fibroblasts triggering changes, including increased proliferation, migration and pro-inflammatory gene expression, all known features of cancer-associated fibroblasts (CAFs). Specifically, melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signalling activation, which reciprocally encourages melanoma growth. Melanosome release inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest an opportunity to block melanoma invasion by preventing the formation of the dermal tumour niche.
AB - Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialized in releasing pigment vesicles, termed melanosomes. In melanoma in situ, we found melanosome markers in distal fibroblasts before melanoma invasion. The melanosomes carry microRNAs into primary fibroblasts triggering changes, including increased proliferation, migration and pro-inflammatory gene expression, all known features of cancer-associated fibroblasts (CAFs). Specifically, melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signalling activation, which reciprocally encourages melanoma growth. Melanosome release inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest an opportunity to block melanoma invasion by preventing the formation of the dermal tumour niche.
UR - http://www.scopus.com/inward/record.url?scp=84983372037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983372037&partnerID=8YFLogxK
U2 - 10.1038/ncb3399
DO - 10.1038/ncb3399
M3 - Article
C2 - 27548915
AN - SCOPUS:84983372037
SN - 1465-7392
VL - 18
SP - 1006
EP - 1017
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 9
ER -