PMID- 34312806
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220405
IS  - 1860-2002 (Electronic)
IS  - 1536-1632 (Print)
IS  - 1536-1632 (Linking)
VI  - 24
IP  - 1
DP  - 2022 Feb
TI  - Molecular Imaging Reveals a High Degree of Cross-Seeding of Spontaneous 
      Metastases in a Novel Mouse Model of Synchronous Bilateral Breast Cancer.
PG  - 104-114
LID - 10.1007/s11307-021-01630-z [doi]
AB  - PURPOSE: Synchronous bilateral breast cancer (SBBC) patients present with cancer 
      in both breasts at the time of diagnosis or within a short time interval. They 
      show higher rates of metastasis and lower overall survival compared to women with 
      unilateral breast cancer. Here we established the first preclinical SBBC model 
      and used molecular imaging to visualize the patterns of metastasis from each 
      primary tumor. PROCEDURES: We engineered human breast cancer cells to express 
      either Akaluc or Antares2 for bioluminescence imaging (BLI) and tdTomato or 
      zsGreen for ex vivo fluorescence microscopy. Both cell populations were implanted 
      into contralateral mammary fat pads of mice (n=10), and dual-BLI was performed 
      weekly for up to day 29 (n=3), 38 (n=4), or 42 (n=3). Primary tumors and lungs 
      were fixed, and ex vivo fluorescence microscopy was used to analyze the cellular 
      makeup of micrometastases. RESULTS: Signal from both Antares2 and Akaluc was 
      first detected in the lungs on day 28 and was present in 9 of 10 mice at 
      endpoint. Ex vivo fluorescence microscopy of the lungs revealed that for mice 
      sacrificed on day 38, a significant percentage of micrometastases were composed 
      of cancer cells from both primary tumors (mean 37%; range 27 to 45%), while two 
      mice sacrificed on day 42 showed percentages of 51% and 70%. CONCLUSIONS: A high 
      degree of metastatic cross-seeding of cancer cells derived from bilateral tumors 
      may contribute to faster metastatic growth and intratumoral heterogeneity. We 
      posit that our work will help understand treatment resistance and optimal 
      planning of SBBC treatment.
CI  - (c) 2021. The Author(s).
FAU - Liu, Shirley
AU  - Liu S
AD  - Robarts Research Institute, University of Western Ontario, London, ON, Canada.
AD  - Department of Medical Biophysics, University of Western Ontario, London, ON, 
      Canada.
FAU - Nystrom, Nivin N
AU  - Nystrom NN
AD  - Robarts Research Institute, University of Western Ontario, London, ON, Canada.
AD  - Department of Medical Biophysics, University of Western Ontario, London, ON, 
      Canada.
FAU - Kelly, John J
AU  - Kelly JJ
AD  - Robarts Research Institute, University of Western Ontario, London, ON, Canada.
FAU - Hamilton, Amanda M
AU  - Hamilton AM
AD  - Robarts Research Institute, University of Western Ontario, London, ON, Canada.
FAU - Fu, Yanghao
AU  - Fu Y
AD  - Robarts Research Institute, University of Western Ontario, London, ON, Canada.
AD  - Department of Medical Biophysics, University of Western Ontario, London, ON, 
      Canada.
FAU - Ronald, John A
AU  - Ronald JA
AUID- ORCID: 0000-0003-3665-173X
AD  - Robarts Research Institute, University of Western Ontario, London, ON, Canada. 
      jronald@robarts.ca.
AD  - Department of Medical Biophysics, University of Western Ontario, London, ON, 
      Canada. jronald@robarts.ca.
LA  - eng
GR  - 377071/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210726
PL  - United States
TA  - Mol Imaging Biol
JT  - Molecular imaging and biology
JID - 101125610
SB  - IM
MH  - Animals
MH  - *Breast Neoplasms/diagnostic imaging/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Mice
MH  - Molecular Imaging
PMC - PMC8760205
OTO - NOTNLM
OT  - Dual bioluminescence imaging
OT  - Metastatic cross-seeding
OT  - Mouse model
OT  - Spontaneous metastases
OT  - Synchronous bilateral breast cancer
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/07/28 06:00
MHDA- 2022/04/05 06:00
PMCR- 2021/07/26
CRDT- 2021/07/27 07:22
PHST- 2021/03/19 00:00 [received]
PHST- 2021/07/05 00:00 [accepted]
PHST- 2021/05/18 00:00 [revised]
PHST- 2021/07/28 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2021/07/27 07:22 [entrez]
PHST- 2021/07/26 00:00 [pmc-release]
AID - 10.1007/s11307-021-01630-z [pii]
AID - 1630 [pii]
AID - 10.1007/s11307-021-01630-z [doi]
PST - ppublish
SO  - Mol Imaging Biol. 2022 Feb;24(1):104-114. doi: 10.1007/s11307-021-01630-z. Epub 
      2021 Jul 26.