Interstitial fluid flow increases invasion of ductal carcinoma in situ-like cells through PI3K-dependent mechanisms

The expression of ErbB2 in pre-invasive cells is a risk factor for invasion and cancer progression. At the same time, interstitial fluid flow is elevated in solid tumors and can modulate tumor cell invasion. The combined role both factors play on invasion has never been studied, especially in the context of how they influence the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Using a technique to apply interstitial fluid flow to cells embedded in a matrix and then measure its effects on cell invasion, we found fluid flow increases the invasion of cells overexpressing ErbB2. This increased invasion is due to the activation of the phosphoinositide 3-kinase (PI3K) and focal adhesion kinase (FAK). This occurs independently of ErbB2 activation. Identifying the mechanisms involved in the progression from DCIS to IDC will provide potential targets for determining appropriate therapy for DCIS patients. This will help improve the current clinical management, decrease patient over-treatment, and prevent cancer-associated deaths.