**Breast Cancer Cell Interaction, Invasion and Metastasis**

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**18** 

Khoo Boon Yin

*Malaysia* 

*Universiti Sains Malaysia, Penang,* 

**The Mesenchymal-Like Phenotype** 

*Institute for Research in Molecular Medicine (INFORMM),* 

Mesenchymal stem cells (MSCs) are progenitor cells that can be isolated from all connective tissues such as bone, adipose, cartilage, blood and muscle (Wang *et al*., 2009). MSCs have recently been described to localise within breast carcinomas where the stem cells integrate into tumour-associated stromal tissues whereby the MSCs promote breast cancer cell invasion and metastasis (Karnoub *et al*., 2007). Previous studies have demonstrated that when combine with weakly metastatic human breast carcinoma cells, bone marrow-derived mesenchymal stem cells (BMSCs) increase the metastatic potency of the cancer cells greatly (Hombauer & Minguell, 2000). This phenomenon was significantly observed in MCF-7 cells where increase in cancer cell proliferation was observed when the cancer cells were co-cultured on the BMSCs feeder layer. Furthermore, light and epifluorescence microscopy studies revealed that the MCF-7 cluster grew in a dispersed fashion on the BMSCs feeder layer due to the decrease expression of adhesive molecules, such as E-cadherin and epithelial-specific antigen (ESA), in the cancer cells. The interaction between the MCF-7 cells and the BMSCs likely causes the loss of the adhesive molecules in the cancer cells. A phenomenon similar to this interaction was also observed in our recent study. Indeed, the study found that the growth of the MCF-7 cells was enhanced not only when the cancer cells were adhesively co-cultured with the BMSCs but

In the adhesive cell interaction, the growth or proliferation rate of the MCF-7 cells, which was measured by colony size, was observed to increase when the cancer cells were cocultured on the BMSCs feeder layer (Fig. 1A and Fig. 1B). The non-adhesive interaction of the MCF-7 cells with BMSCs was also found to increase the growth of the cancer cells. When the cancer cells were incubated with the conditioned medium (culture supernatant) of the BMSCs, the proliferation rate of the MCF-7 cells increased approximately 16.6% when compared to the proliferation rate of the cancer cells incubated with growth medium only (Fig. 1C). This phenomenon indicates that the increase in the proliferation rate of the cancer cells due to the presence of the BMSCs must not be related to a direct physical cell–cell interaction, as similar findings are observed in both the adhesive and non-adhesive co-

Note: In this chapter, adhesive co-culture is defined as the growth of cancer cells on a nontumorigenic cell monolayer where direct physical cell–cell interaction occurs. Non-adhesive

**1. Introduction** 

culture conditions.

also when they were co-cultured non-adhesively.

**of the MDA-MB-231 Cell Line** 
