COX-2 level is significantly lower in nevi than in melanomas, increases gradually with progression of these malignant cancers and reaches the highest values in metastases.
COX-2 expression was not correlated with age, gender, tumor location, cancer histology, or necrosis (<i>P </i>><i> </i>0.1), but was significantly associated with tumor grade (high grade vs. low grade: OR = 4.81, <i>P </i><<i> </i>0.001), clinical stage (stage 3-4 vs. stage 1-2: OR = 4.89, <i>P </i><<i> </i>0.001), and metastasis (yes vs. no: OR = 3.53, <i>P </i><<i> </i>0.001).
COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells.
The present study aimed to investigate the mechanism by which cyclooxygenase‑2 (COX‑2) promotes the metastasis of MG‑63 osteosarcoma cells through the PI3K/AKT/NF‑κB pathway.
In addition, GR agonist treatment or miR-708 mimic transfection remarkably inhibited IKKβ expression and suppressed nuclear factor-kappaB (NF-κB) activity and its downstream target genes, including COX-2, cMYC, cyclin D1, Matrix metalloproteinase (MMP)-2, MMP-9, CD24, CD44 and increased p21CIP1 and p27KIP1 that are known to be involved in proliferation, cell-cycle progression, metastasis and CSC marker protein.
It suppressed the expression of NF-κB and NF-κB-regulated gene products such as COX-2, survivin and MMP-9 which are involved in the regulation of different processes like proliferation, survival, invasion, and metastasis of OSCC cells.
The cytokine-mediated upregulation of metastasis- and inflammatory-associated genes, which are downstream genes of STAT3 including the intercellular adhesion molecule-1, matrix metalloproteinase-9, inducible nitric oxide synthase, and cyclo-oxygenase 2 (COX-2), were also significantly abolished by myricetin treatment.
Further study suggested that AKT1 and cyclooxygenase-2 (COX2; PTGS2) might mediate the CXCR2 signaling to inversely control the breast cancer metastasis and chemoresistance through the regulation of EMT, apoptosis, and senescence.
Tumor-promoting genes correlated with the expression of COX1, COX2, and ALOX5 are known to effectively increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the pathogenesis of breast cancer.
In addition, we observed a decrease in COX2 expression levels in LN metastasis compared to the corresponding primary tumors, reinforcing the idea that the immune escape mechanism is impaired in the microenvironment of thyroid LN metastasis.
Drug treatment also significantly abrogated presurgical increases in serum IL6 and C-reactive protein levels, abrogated perioperative declines in stimulated IL12 and IFNγ production, abrogated postoperative mobilization of CD16<sup>-</sup> "classical" monocytes, and enhanced expression of CD11a on circulating natural killer cells.<b>Conclusions:</b> Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer.<i></i>.
Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.
The role of SPARC in metastasis involved a COX-2-independent enhancement of cell disengagement from the primary tumor and adherence to the lungs that fostered metastasis implantation.
We reported previously that human fibroblasts release 5-methoxytryptophan (5-MTP) which inhibits cancer cell COX-2 overexpression and suppresses cancer cell migration and metastasis.
Metastasis-free survival (MFS) was significantly better in patients with high COX-2 expression level, the prognosis of whom was similar to patients with PIK3CA mutations.