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**24** 

*Canada* 

Anthony Magliocco and Cay Egan

*University of Calgary* 

**Breast Cancer Metastasis: Advances Through** 

**the Use of In Vitro Co-Culture Model Systems** 

Worldwide, breast cancer is the most frequent cancer diagnosed in women and is the second-most leading cause of cancer related deaths in women (Jemal, Bray et al. 2011). Death from breast cancer is most often the result of the spread of the primary tumour to distant sites, where the cancer cells lodge and develop into metastases. Depending on the site of the metastasis, the patient may live for years with reduced quality of life and needing increased health care resources. There is clearly a need for a greater understanding of the molecular events involved in breast cancer metastasis in order to improve treatment options for breast cancer patients and develop therapies aimed at preventing breast cancer

Here we will summarize what is known about the molecular basis of breast cancer metastasis and discuss the use of *in vivo* and primarily *in vitro* model systems to study it.

As early as 1889, Stephen Paget observed that some cancers metastasized preferentially to specific organs, and developed his theory of "seed and soil"(Paget 1889). The essential tenet of this theory was that cancer cells (seeds) disseminate throughout the body from their point of origin but can only develop metastatic satellites in appropriate stromal environments (soils). The many advances in our understanding of the molecular and cellular bases of breast cancer metastasis has led to a somewhat more complex picture, and the processes involved are still not completely understood. Breast cancer can spread to any secondary site in the body but metastases appear preferentially in bone, lung and liver (Rabbani and Mazar 2007). Presumably these sites provide a microenvironment favourable for the growth and

There are two prevailing models of breast cancer metastasis; one suggesting a linear progression and the other a parallel progression. The linear progression model advances the idea that cells in the primary tumour accumulate progressive mutations in a stepwise manner in genes regulating some aspect of cell growth and division such as oncogenes and tumour suppressor genes. Some cells eventually become able to proliferate autonomously; they expand clonally and leave the primary site to travel through lymphatic or vascular systems to a distant organ where they develop into a secondary metastatic growth. This

development of breast cancer cells (Nguyen, Bos et al. 2009).

**1. Introduction** 

metastasis.

**2.1 Metastasis** 

**2. Current knowledge** 

