TY - JOUR
T1 - Live Cell Lineage Tracing of Dormant Cancer Cells
AU - Kim, Hyuna
AU - Wirasaputra, Anna
AU - Mohammadi, Farnaz
AU - Kundu, Aritra Nath
AU - Esteves, Jennifer A.E.
AU - Heiser, Laura M.
AU - Meyer, Aaron S.
AU - Peyton, Shelly R.
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Breast cancer is a leading cause of global cancer-related deaths, and metastasis is the overwhelming culprit of poor patient prognosis. The most nefarious aspect of metastasis is dormancy, a prolonged period between primary tumor resection and relapse. Current therapies are insufficient at killing dormant cells; thus, they can remain quiescent in the body for decades until eventually undergoing a phenotypic switch, resulting in metastases that are more adaptable and drug resistant. Unfortunately, dormancy has few in vitro models, largely because lab-derived cell lines are highly proliferative. Existing models address tumor dormancy, not cellular dormancy, because tracking individual cells is technically challenging. To combat this problem, a live cell lineage approach to find and track individual dormant cells, distinguishing them from proliferative and dying cells over multiple days, is adapted. This approach is applied across a range of different in vitro microenvironments. This approach reveals that the proportion of cells that exhibit long-term quiescence is regulated by both cell intrinsic and extrinsic factors, with the most dormant cells found in 3D collagen gels. This paper envisions that this approach will prove useful to biologists and bioengineers in the dormancy community to identify, quantify, and study dormant tumor cells.
AB - Breast cancer is a leading cause of global cancer-related deaths, and metastasis is the overwhelming culprit of poor patient prognosis. The most nefarious aspect of metastasis is dormancy, a prolonged period between primary tumor resection and relapse. Current therapies are insufficient at killing dormant cells; thus, they can remain quiescent in the body for decades until eventually undergoing a phenotypic switch, resulting in metastases that are more adaptable and drug resistant. Unfortunately, dormancy has few in vitro models, largely because lab-derived cell lines are highly proliferative. Existing models address tumor dormancy, not cellular dormancy, because tracking individual cells is technically challenging. To combat this problem, a live cell lineage approach to find and track individual dormant cells, distinguishing them from proliferative and dying cells over multiple days, is adapted. This approach is applied across a range of different in vitro microenvironments. This approach reveals that the proportion of cells that exhibit long-term quiescence is regulated by both cell intrinsic and extrinsic factors, with the most dormant cells found in 3D collagen gels. This paper envisions that this approach will prove useful to biologists and bioengineers in the dormancy community to identify, quantify, and study dormant tumor cells.
KW - Matrigel
KW - biomaterials
KW - breast cancer
KW - collagen
KW - poly(ethylene glycol) hydrogels
UR - http://www.scopus.com/inward/record.url?scp=85147043691&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147043691&partnerID=8YFLogxK
U2 - 10.1002/adhm.202202275
DO - 10.1002/adhm.202202275
M3 - Article
C2 - 36625629
AN - SCOPUS:85147043691
SN - 2192-2640
VL - 12
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 14
M1 - 2202275
ER -