Breast Cancer

Breast cancer represents the second leading cause of cancer death in women. It is projected that more than 230,000 new cases of breast cancer will be diagnosed this year. While death rates have been declining since 1989, breast cancer will result in about 40,000 deaths this year. The reductions in mortality rates are a result of better screening techniques, earlier detection, and improved treatment; however, 1 in 5 survivors will relapse within 10 years of treatment.

 

Indication Cell Line Available Models
Breast Carcinoma MDA-MB-231, MDA-MB-468, 4T1 Xenograft, Orthotopic, Syngeneic, In Vitro Assays, Cancer Stem Cells

 

Preclinical Models

Model Description Length Endpoints
Xenograft Tumor cells are implanted subcutaneously in rats or mice Variable Tumor volume, histology, cytokine induction, protein, and RNA expression.
Orthotopic Cells are implanted directly into the desired organ site in rats or mice
Syngeneic Cells are from the same species as  host and are immunocompatible therefore immunocompetent animals can be used.
Cancer Stem Cells Tumor initiating cells are enriched from a heterogeneous bulk tumor cell population.  Cancer stem cells are studied in comparison to the “parent” line and can be assessed in 3-D culture in vitro or implanted into animals in vivo.  In vitro: Tumorsphere Formation, Proliferation, Survival, Migration, FACS profile.
In Vivo: Tumor volume, metastasis, histology, cytokine induction, protein and RNA Expression
In Vitro Assays Assays for: Proliferation and survival, migration and invasion, tumorspheres/colony formation, and FACS biomarker analysis Tumor cell growth, invasiveness and survival
* Several models are compatible with IVIS imaging for in-life monitoring of disease progression.

 

Xenograft Model of Breast Cancer

BreastCancer

Representative growth curve of a triple negative breast cancer cell line (MD-468) grown as a Xenograft with standard of care

Orthotopic (non-syngeneic) Model of Breast Cancer

Orthotopic_Breat

 

(A) Representative IVIS images of orthotopic tumor growth in the mammary gland derived from the triple negative breast cancer cell line MDA-MB-231 treated with combinations of standard of care agents on day 11 and Day 39. (B) Radiance values for each group showing growth trends over the course of the study.

Syngeneic Model of Breast Cancer

Tumor-Growth

 

4T1 cells were injected into the 4th mammary fat pad of Balb/c mice. Once tumors reached ~90mm3, animals were treated as indicated above.

SyngeneicModelBreast2

 

(A)Representative IVIS Images Showing the Treatment Effects of Dosing with 5-FU on 4T1 Mammary Orthotopic Tumor Growth (B) Radiance values for each animal are quantitated and the average radiance presented to demonstrate the efficacy of therapeutics in treating mammary tumors.

SyngeneicModelBreastCancer5002

 

Primary mammary tumor growth and associated lung metastases. (A) Primary tumor from 4T1 cells orthotopically injected into the 4th mammary fat pad of Balb/c mice (B,C) H&E staining of two examples of primary mammary tumors. (D) Image of lung metastases with (E,F) accompanying H&E staining. (B,E) and (C,F) are images from the same animal demonstrating the morphological similarities of tumor cells between primary tumors and lung metastases.

Cancer Stem Cell Model of Breast Cancer

 

stem-Cell2

 

(A) Representative IVIS images of orthotopic tumor growth of cancer stem cells in the mammary gland derived from the triple negative breast cancer cell line MDA-MB-231 treated with combinations of standard of care agents on day 11 and Day 39. (B) Radiance values for each group showing growth trends over the course of the study.

cancer-stem-cells

 

Cancer stem cells were enriched from “parent line” MDA-MB-231 cells using positive selection for the CD44+ population. The left panel shows the FACS profile of stem cell markers CD44+, CD133+ and CD24- on this enriched population. The middle panel shows the differences in proliferation rates between the parent line and the enriched cancer stem cells. The panel on the right represents differences in invasive migration between the parent line and the enriched cancer stem cells.