**3.4 LYVE-1**

HA links the two main functions of the lymphatic system: draining of interstitial fluids and immune surveillance. These functions are achieved through its interaction with the receptor LYVE-1, present in lymphatic endothelia (Jackson, 2009). LYVE-1 is a type I integral membrane polypeptide that exhibits high homology with CD44 (Banerji *et al*., 1999) and is a homeostatic HA receptor required for liver and lymphatic vessel formation. Its expression does not change as frequently in malignancy as HA receptors involved in response to injury, for example CD44 and RHAMM/HMMR. This does not rule out a role in injury and tumour progression however, as lymphangiogenesis is an important processes in both events, and elevated accumulation of HA in stroma results in lymphangiogenesis *via* signalling through LYVE-1 (Gale *et al*., 2007).

To further demonstrate the association of LYVE-1 with tumour dissemination through the lymphatic system, (Du *et al*., 2010) expressed LYVE-1 in COS-7 kidney cells and performed cell adhesion assays with the BCA cell line HS-578T which produces HA. These two cell lines had enhanced adhesion over the control cells, COS-7 not expressing LYVE-1. This

tumour cell migration/infiltration. The human BCA cell line MDA-MB-231 expresses mainly TLR4, and siRNA mediated knock-down of TLR4 significantly reduces cell survival and expression of the cytokines Il-6 and Il-8, suggesting that TLR4 is a promising target for

Fig. 3. HA initiates the signalling of RHAMM and CD44 regulated pathways, resulting in a

HA links the two main functions of the lymphatic system: draining of interstitial fluids and immune surveillance. These functions are achieved through its interaction with the receptor LYVE-1, present in lymphatic endothelia (Jackson, 2009). LYVE-1 is a type I integral membrane polypeptide that exhibits high homology with CD44 (Banerji *et al*., 1999) and is a homeostatic HA receptor required for liver and lymphatic vessel formation. Its expression does not change as frequently in malignancy as HA receptors involved in response to injury, for example CD44 and RHAMM/HMMR. This does not rule out a role in injury and tumour progression however, as lymphangiogenesis is an important processes in both events, and elevated accumulation of HA in stroma results in lymphangiogenesis *via*

To further demonstrate the association of LYVE-1 with tumour dissemination through the lymphatic system, (Du *et al*., 2010) expressed LYVE-1 in COS-7 kidney cells and performed cell adhesion assays with the BCA cell line HS-578T which produces HA. These two cell lines had enhanced adhesion over the control cells, COS-7 not expressing LYVE-1. This

BCA therapy (Yang *et al.*, 2010).

variety of pro-tumourigenic outcomes.

signalling through LYVE-1 (Gale *et al*., 2007).

**3.4 LYVE-1** 

suggests that LYVE-1 plays a role in tumour cell adhesion which is dependent on HA-LYVE-1 interaction. Apart from its effect on tumour cell adhesion, LYVE-1 has also been proven to be a prognostic factor in tongue squamous cell carcinoma and decreased levels of LYVE-1 in the invasive front of tumours predicts cervical lymph node metastasis (Matsumoto *et al*., 2010).
