Tumor Microenvironment Regulates Metastasis and Metastasis Genes of Mouse MMTV-PymT Mammary Cancer Cells In Vivo

Werbeck, Jillian L.; Thudi, Nanda K.; Martin, Chelsea K.; Premanandan, Christopher; Yu, Lianbo; Ostrowksi, M. C.; Rosol, Thomas J.

doi:10.1177/0300985813505116

Cited by 28 publications

(34 citation statements)

References 68 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). 164 Each injection technique has advantages and disadvantages that must be considered depending on the particular study and hypothesis to be tested. 164 …”

Section: In Vivo Injection Techniques Used To Induce Bone Metastasismentioning

confidence: 99%

See 1 more Smart Citation

Animal Models of Bone Metastasis

et al. 2015

Self Cite

View full text Add to dashboard Cite

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

show abstract

“…1). 164 Each injection technique has advantages and disadvantages that must be considered depending on the particular study and hypothesis to be tested. 164 …”

Section: In Vivo Injection Techniques Used To Induce Bone Metastasismentioning

confidence: 99%

“…Finally, intraosseous injections model the ability to grow in and modify the bone microenvironment. Reprinted from Werbeck et al 164 …”

Section: Figurementioning

confidence: 99%

Animal Models of Bone Metastasis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…If the expression of TIE2 is lost or reduced in the primary tumor, it seems, however, that it can be restored or increased at the site of bone metastases. Werbeck et al compared gene expression at different sites of tumors caused by Met-1 cells, derived from the primary tumor of a MMTV-PyMT mouse [48]. Levels of TIE2 mRNA were higher in Met-1 cells in the lungs and the adrenal glands, and significantly higher in cells growing in the tibia (3.8-fold, p = 0.03), compared to cells inoculated in the mammary fat pad [48].…”

Section: Discussionmentioning

confidence: 99%

TIE2 Induces Breast Cancer Cell Dormancy and Inhibits the Development of Osteolytic Bone Metastases

Drescher

Juàrez

Arellano

et al. 2020

Cancers

View full text Add to dashboard Cite

Breast cancer (BCa) cells disseminating to the bone can remain dormant and resistant to treatments for many years until relapsing as bone metastases. The tyrosine kinase receptor TIE2 induces the dormancy of hematopoietic stem cells, and could also induce the dormancy of BCa cells. However, TIE2 is also a target for anti-angiogenic treatments in ongoing clinical trials, and its inhibition could then restart the proliferation of dormant BCa cells in bone. In this study, we used a combination of patient data, in vitro, and in vivo models to investigate the effect of TIE2 in the dormancy of bone metastases. In BCa patients, we found that a higher TIE2 expression is associated with an increased time to metastases and survival. In vitro, TIE2 decreased cell proliferation as it increased the expression of cyclin-dependent kinase inhibitors CDKN1A and CDKN1B and arrested cells in the G0/G1 phase. Expression of TIE2 also increased the resistance to the chemotherapeutic 5-Fluorouracil. In mice, TIE2 expression reduced tumor growth and the formation of osteolytic bone metastasis. Together, these results show that TIE2 is sufficient to induce dormancy in vitro and in vivo, and could be a useful prognostic marker for patients. Our data also suggest being cautious when using TIE2 inhibitors in the clinic, as they could awaken dormant disseminated tumor cells.

show abstract

“…Intracardiac injection requires ultrasound guided imaging of the injection site or other imaging modalities such as bioluminescence of luciferase tagged cells to confirm successful injection. Tumor cell injection via the left ventricle may result in bone, brain, lung, and/or liver metastasis, amongst other organs [44][45][46][47][48] . Because of multi-organ metastases, these mice frequently need to be euthanized prior to development of overt liver metastasis, negating the ability to fully investigate metastatic growth within the liver.…”

Section: P53mentioning

confidence: 99%

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

Goddard

Fischer

Schedin

2016

JoVE

View full text Add to dashboard Cite

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 -15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 -10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 -40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas.

show abstract

Tumor Microenvironment Regulates Metastasis and Metastasis Genes of Mouse MMTV-PymT Mammary Cancer Cells In Vivo

Cited by 28 publications

References 68 publications

Animal Models of Bone Metastasis

Animal Models of Bone Metastasis

TIE2 Induces Breast Cancer Cell Dormancy and Inhibits the Development of Osteolytic Bone Metastases

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

Contact Info

Product

Resources

About