Effects of chronic indomethacin therapy on the development and progression of spontaneous mammary tumors in C3H/HEJ mice

COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

“…The stimulatory role of COX-2 in breast cancer progression has earlier been explained by multiple PGE 2 -dependent mechanisms: an inactivation of antitumour immune cells (Lala and Saarloos, 1994), a stimulation of cancer cell growth and survival (Basu et al, 2005), migration (Rozic et al, 2001;Timoshenko et al, 2003), invasiveness (Rozic et al, 2001) and angiogenesis (Lala et al, 1997;Rozic et al, 2001). Present study demonstrates an additional role of COX-2-in human breast cancer: a stimulation of VEGF-C and thereby lymphangiogenesis in situ, also reported recently for nonsmall cell lung cancer cells (Su et al, 2004).…”

“…A functional role of COX-2 in tumour development and progression has been demonstrated by both overexpression (Liu et al, 2001) and disruption (Chulada et al, 2000) of the COX-2 gene as well as application of drugs blocking both COX-1/-2 or COX-2 alone (Lala et al, 1997;Harris, 2003;Wang and DuBois, 2004). This role has primarily been attributed to elevated levels of prostanoids, mainly prostaglandin E 2 (PGE 2 ), in the tumour microenvironment (Rolland et al, 1980).…”

“…This role has primarily been attributed to elevated levels of prostanoids, mainly prostaglandin E 2 (PGE 2 ), in the tumour microenvironment (Rolland et al, 1980). We had earlier demonstrated that tumourderived PGE 2 acts as a paracrine as well as an autocrine factor to promote breast cancer progression and metastasis by multiple mechanisms, namely by inactivation of host anti tumour immune cells and a stimulation of tumour cell migration, invasiveness and tumour-associated angiogenesis (Lala and Saarloos, 1994;Lala et al, 1997;Rozic et al, 2001).…”

Targeting COX-2 and EP4 to control tumor growth, angiogenesis, lymphangiogenesis and metastasis to the lungs and lymph nodes in a breast cancer model

“…10 In a case-control study in women, use of selective COX-2 inhibitors was associated with a 71% reduction in breast cancer risk. 11 Our laboratory had shown that tumor-derived PGE2 frequently resulting from elevated COX-2 expression promotes breast cancer progression by multiple mechanisms: an inactivation of host antitumor immune cells, 12 a stimulation of tumor cell migration, invasiveness and tumor-associated angiogenesis [13][14][15][16] as well as lymphangiogenesis resulting from an upregulation of vascular endothelial growth factor (VEGF)-C, 17 thereby promoting lymphatic metastasis. In these studies, COX-2-mediated promotion of migratory, 15 invasive 16 and VEGF-C upregulatory 17 functions were at least in part due to stimulation of PGE receptors prostaglandin E (EP)4, and to a minor extent EP1, expressed by breast cancer cells.…”

Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

“…The effects of NSAIDs in other cancers have also been extensively studied in the last decade. Nonsteroidal anti-inflammatory drugs have been shown to prevent breast cancer in animal models (Lala et al, 1997;Robertson et al, 1998). Proposed mechanisms commonly involve the inhibition of cyclooxygenase-2 (COX-2) (Sjodahl, 2001), the enzyme responsible for the production of various prostaglandins that play a key role in the proliferation of tumour tissue; there is accumulating evidence that NSAIDs may have the ability to restore apoptosis and inhibit angiogenesis (Thun et al, 2002).…”