The Effect of Stromal Integrin β3-Deficiency on Two Different Tumors in Mice

Abstract

There is an increasing focus on the tumor microenvironment in carcinogenesis. Integrins are important receptors and adhesion molecules in this environment and have been shown to be involved in cell adhesion, proliferation, differentiation and migration. The present study aimed to evaluate the effect of stromal integrin β3-deficiency on tumor growth, angiogenesis, interstitial fluid pressure (PIF), fibrosis and metastasis in a murine breast cancer (4T1) and a prostate tumor (RM11) model. We showed that stromal integrin β3-deficiency led to an elevation in PIF that correlated to a shift towards thicker collagen fibrils in the 4T1 mammary tumor. In the RM11 prostate carcinoma model there was no effect of integrin β3-deficiency on PIF and collagen fibril thickness. These findings support the notion that changes in the collagen scaffold influence PIF, and also indicate that there must be important crosstalk between the stroma and tumor cells, in a tumor cell line specific manner. Furthermore, stromal integrin β3-deficiency had no effect on tumor growth or angiogenesis in both tumor models and no effect on lung metastasis in the 4T1 mammary tumor model. In conclusion, the stromal β3 integrin influence PIF, possibly via its effect on the structure of the collagen network, in a tumor cell line dependent manner.

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

“…In addition to poor lymphatic drainage, high TIP is also a result of these abnormal blood vessels, which leak fluid and proteins into the area between tumor cells (Stohrer et al, 2000). Direct measurements from a large sample of human (Chaudary et al, 2012;Milosevic et al, 2001;Nathanson and Nelson, 1994;Taghian et al, 2005;Willett et al, 2004) and animal (Chaudary et al, 2012;Ferretti et al, 2009;Geretti et al, 2015;Halldorsdottir et al, 2017;Heine et al, 2012;Kłosowska-Wardega et al, 2009;Lunt et al, 2008;Murakami et al, 2013;Pietras et al, 2002;Reigstad et al, 2016) subjects have demonstrated that interstitial pressure was found to be 5À30 mm Hg higher in cancerous tissue compared to normal tissue, although values exceeding 100 mm Hg have been recorded. Noteworthy, elevated TIP levels reduce blood flow and compromise anticancer drug delivery (Jain, 1994).…”

MDA‐MB‐231 and 8701BC breast cancer lines promote the migration and invasiveness of ECV304 cells on 2D and 3D type‐I collagen matrix

“…Molecular analysis performed using conditioned media showed that two analyzed cancer cell lines affect ECV304 cells stimulating a different expression of angiogenic factors. MDA‐MB‐231 triple‐negative breast cancer cell line, unlike 8701BC ductal infiltrating cell line, increases in ECV304 cells the expression of VEGFA, the strongest pro‐angiogenic factor; and the β3‐integrin, marker of epithelium–mesenchyme transition (Reigstad et al, ). The same cancer line stimulates endothelial activity of the serine‐protase CD26/DPP4.…”