PMID- 34496353
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 1758-5090 (Electronic)
IS  - 1758-5082 (Linking)
VI  - 13
IP  - 4
DP  - 2021 Sep 21
TI  - Sporadic cell death in macroscale 3D tumor grafts with high drug resistance by 
      activating cell-ECM interactions.
LID - 10.1088/1758-5090/ac24dd [doi]
AB  - In the tumor microenvironment (TME), the extracellular matrix (ECM) provides a 
      dynamic structure for cell adhesion and cancer cell motility, such as migration 
      and invasion, as well as remodeling. Matrix metalloproteinases (MMPs) promote 
      cancer cell motility, which contributes to inducing drug resistance and thereby 
      acquiring aggressive features. The drug resistance-induced 3Din vitrotumor model 
      can be an effective model for therapeutic strategies for anticancer drugs 
      targeting aggressive cancer cells. Here, we describe highly drug-resistant 
      multicellular tumoroids (MCTs)-ECM tumor grafts under a macroscale dense 3Din 
      vitromodel through a combination of numerous MCTs and a collagen matrix. MCTs-ECM 
      tumor grafts promote the high activity of MMP2 and MMP9 compared to general MCTs 
      and induced cancer cell motility. Then, after the administration of anticancer 
      drugs, the tumor grafts show increased drug resistance, with both the sporadic 
      distribution of necrotic cells and the reduction of apoptotic portions, by 
      activating cancer cell motility. MCTs-ECM tumor graft could be useful as a 
      macroscale tumor graft model for inducing drug resistance by activating cancer 
      cell motility and evaluating the efficacy of anticancer drugs targeting cancer 
      with aggressive features.
CI  - Creative Commons Attribution license.
FAU - Lee, Sang Woo
AU  - Lee SW
AUID- ORCID: 0000-0001-9913-0638
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, Seoul, Republic of Korea.
FAU - Park, Se Eun
AU  - Park SE
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, Seoul, Republic of Korea.
FAU - Jeong, Gi Seok
AU  - Jeong GS
AUID- ORCID: 0000-0002-2584-9129
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, Seoul, Republic of Korea.
AD  - Department of Convergence Medicine, University of Ulsan College of Medicine, 
      Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210921
PL  - England
TA  - Biofabrication
JT  - Biofabrication
JID - 101521964
SB  - IM
MH  - Cell Death
MH  - Drug Resistance
MH  - *Extracellular Matrix
MH  - Humans
MH  - *Neoplasms/drug therapy
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - 3D tumor graft
OT  - cell-ECM interaction
OT  - drug resistance
OT  - extracellular matrix (ECM)
OT  - macroscale
EDAT- 2021/09/09 06:00
MHDA- 2021/11/10 06:00
CRDT- 2021/09/08 20:10
PHST- 2021/06/09 00:00 [received]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/09/09 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2021/09/08 20:10 [entrez]
AID - 10.1088/1758-5090/ac24dd [doi]
PST - epublish
SO  - Biofabrication. 2021 Sep 21;13(4). doi: 10.1088/1758-5090/ac24dd.