Tumor cells are exposed to interstitial flow through leaky capillaries that imposes fluid shear stress on their surfaces (Figure 1). Enhanced interstitial flow shear stress on tumor cells has been shown to increase cell motility that contributes to enhanced cell migration of metastatic cells and suppressed migration of non-metastatic cells as first shown by our group (Qazi et al., 2011, 2013).

Figure 1. Schematic diagram showing interstitial flow across a tumor microvessel exposing tumor cells to fluid shear stress. The microvessels of tumors becomes tortuous and leaky leading to enhanced interstitial flow compared to tissues with normal microvessels.

Figure 1. Schematic diagram showing interstitial flow across a tumor microvessel exposing tumor cells to fluid shear stress. The microvessels of tumors becomes tortuous and leaky leading to enhanced interstitial flow compared to tissues with normal microvessels.

 

Recent work from our lab (Qazi et al., 2013) visualized a distinct surface glycocalyx layer on tumor cells in vitro (Figure 2).  We showed that the glycocalyx is a mechanotransducer for interstitial flow shear stress on tumor cells by observing that the enhanced cell migration induced by interstitial flow is blocked by removal of glycocalyx components with enzymes (Figure 3).

Figure 2. Fluorescent imaging of heparan sulfate (green) around SN12L1 metastatic kidney carcinoma cells in a collagen I gel (left). The heparan sulfate could be removed by treatment with heparanase (right). Blue is DAPI staining of the nuclei. (Qazi et al., 2013)

Figure 2. Fluorescent imaging of heparan sulfate (green) around SN12L1 metastatic kidney carcinoma cells in a collagen I gel (left). The heparan sulfate could be removed by treatment with heparanase (right). Blue is DAPI staining of the nuclei. (Qazi et al., 2013)

 

Figure 3. Migration of SN12L1 metastatic kidney carcinoma cells is enhanced by interstitial flow (values normalized by non-flow companion controls). This enhancement is blocked by removal of glycocalyx components with enzymes. (Qazi et al., 2013)

Figure 3. Migration of SN12L1 metastatic kidney carcinoma cells is enhanced by interstitial flow (values normalized by non-flow companion controls). This enhancement is blocked by removal of glycocalyx components with enzymes. (Qazi et al., 2013)