PMID- 34572807
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 18
DP  - 2021 Sep 12
TI  - 3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition 
      into a Tumor-Promoting Phenotype.
LID - 10.3390/cancers13184579 [doi]
LID - 4579
AB  - Tumor immune response is shaped by the tumor microenvironment (TME), which often 
      evolves to be immunosuppressive, promoting disease progression and metastasis. An 
      important example is melanoma tumors, which display high numbers of 
      tumor-associated macrophages (TAMs) that are immunosuppressive but also have the 
      potential to restore anti-tumor activity. However, to therapeutically target 
      TAMs, there is a need to understand the early events that shape their 
      tumor-promoting profile. To address this, we built and optimized 3D in vitro 
      co-culture systems, composed of a collagen-I matrix scaffolding murine 
      bone-marrow-derived macrophages (BMDMs), YUMM1.7 melanoma cells, and fibroblasts 
      to recreate the early melanoma TME and study how interactions with fibroblasts 
      and tumor cells modulate macrophage immune activity. We monitored BMDM behavior 
      and interactions through time-lapse imaging and characterized their activation 
      and secretion. We found that stromal cells induced a rapid functional activation, 
      with increased motility and response from BMDMs. Over the course of seven days, 
      BMDMs acquired a phenotype and secretion profile that resembled melanoma TAMs in 
      established tumors. Overall, the direct cell-cell interactions with the stromal 
      components in a 3D environment shape BMDM transition to a TAM-like 
      immunosuppressive state. Our systems will enable future studies of changes in 
      macrophage-stromal cross-talk in the melanoma TME.
FAU - Pizzurro, Gabriela A
AU  - Pizzurro GA
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Bridges, Kathryn
AU  - Bridges K
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Alexander, Amanda F
AU  - Alexander AF
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Huang, Alice
AU  - Huang A
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Baskaran, Janani P
AU  - Baskaran JP
AUID- ORCID: 0000-0002-4764-9611
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Ramseier, Julie
AU  - Ramseier J
AUID- ORCID: 0000-0002-6383-9837
AD  - Department of Dermatology, Yale University, New Haven, CT 06511, USA.
FAU - Bosenberg, Marcus W
AU  - Bosenberg MW
AD  - Department of Dermatology, Yale University, New Haven, CT 06511, USA.
AD  - Department of Pathology, Yale University, New Haven, CT 06511, USA.
AD  - Department of Immunobiology, Yale University, New Haven, CT 06511, USA.
FAU - Mak, Michael
AU  - Mak M
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
FAU - Miller-Jensen, Kathryn
AU  - Miller-Jensen K
AD  - Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
AD  - Department of Molecular, Cellular and Developmental Biology, Yale University, New 
      Haven, CT 06511, USA.
LA  - eng
GR  - P50 CA121974/CA/NCI NIH HHS/United States
GR  - R01 CA216101/CA/NCI NIH HHS/United States
GR  - U01 CA238728/CA/NCI NIH HHS/United States
GR  - Melanoma Research Grant/Harry J. Lloyd Charitable Trust/
PT  - Journal Article
DEP - 20210912
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8471848
OTO - NOTNLM
OT  - 3D culture
OT  - fibroblasts
OT  - immunosuppression
OT  - melanoma
OT  - tumor microenvironment
OT  - tumor-associated macrophages
OT  - type I collagen
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/09/29 06:01
PMCR- 2021/09/12
CRDT- 2021/09/28 01:07
PHST- 2021/08/03 00:00 [received]
PHST- 2021/08/30 00:00 [revised]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/09/28 01:07 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/09/29 06:01 [medline]
PHST- 2021/09/12 00:00 [pmc-release]
AID - cancers13184579 [pii]
AID - cancers-13-04579 [pii]
AID - 10.3390/cancers13184579 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Sep 12;13(18):4579. doi: 10.3390/cancers13184579.