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.
We examined the effects of the preferential cyclooxygenase-2 (COX-2) inhibitor celecoxib on tumorigenesis, angiogenesis, apoptosis, vascular endothelial growth factor (VEGF) protein expression and metastasis in HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum.
We correlated the cyclooxygenase-2 overexpression with the chromosomal gain of 1q25.2-q25.3 and patients survival and compared primary colorectal cancers and their paired metastases at the DNA and protein level.
VEGF-C and VEGF-D were thought to exhibit similar bioactivities, yet recent studies indicated distinct signaling mechanisms (e.g. tumor-derived VEGF-C promoted expression of the prostaglandin biosynthetic enzyme COX-2 in lymphatics, a response thought to facilitate metastasis via the lymphatic vasculature, whereas VEGF-D did not).
VEGF-C and its VEGFR-3 played a crucial role in the regulation of tumor growth and metastasis in cervical cell lines, and COX-2 might be a regulator of VEGF-C expression.
Upregulation of cyclooxygenase-2 (COX-2) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor.
Treatment of KB/COX-2 with COX-2 small interfering RNA (siRNA) inhibited the colony formation but not cell growth in vitro, and suppressed tumorigenicity and hematogenous metastasis in nude mice.
To understand the functional effects of COX-2 silencing underlying the inhibition of tumor growth and metastasis previously reported, we investigated changes in these cells for a number of cancer-associated phenotypes.
To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.
To elucidate the mechanisms by which exacerbated COX2 expression potentiates metastasis we genetically manipulated non-metastatic mammary tumor cells (TM40D) to over-express COX2 (TM40D-COX2).
This inhibition correlated with the suppression of NF-kappaB-dependent genes involved in anti-apoptosis (IAP-1, IAP-2, XIAP, Bcl-2, and Bcl-xL), cell proliferation (c-Myc, COX-2, and cyclin D1), and metastasis (VEGF and MMP-9).
These results demonstrate the ability of HBx to promote tumor cell invasion by a mechanism involving the upregulation of MT1-MMP and COX-2 and provide new insights into the mechanism of action of this viral protein and its involvement in tumor metastasis and recurrence of hepatocellular carcinoma.
These new functional roles of COX-2 may identify new biomarkers and new targets for use in combination with COX-2 targeting to prevent invasion and metastasis.
These findings suggest that inhibition of COX-2 development may lead not only to inhibition of the proliferation and metastasis of prostate carcinoma but also to the inhibition of prostate carcinogenesis.
These data suggest that the profound effects of COX-2 silencing on inhibiting invasion, tumor growth and metastasis from MDA-MB-231 cells are dependent on the induction of IL-1beta-dependent COX-2 and HIF-1alpha but are independent of hypoxia
These data expand upon the roles of COX-2 in shaping the structure and function of the ECM in primary and metastatic tumors, and identify the potential role of COX-2 in modifying the number of CAFs in tumors that may have contributed to the altered ECM.
These data collectively imply COX-2 may play an important role during premalignant hyperproliferation, as well as the later stages of invasive carcinoma and metastasis in various human epithelial cancers.
Therefore, to investigate whether COX2 is important for breast cancer metastasis in humans, we analyzed COX2 protein expression by immunostaining of primary tumors from 112 operable stages I, II, or III patients and determined its correlation with bone marrow micrometastasis (BMM).
Therefore, the results suggest that proton beam irradiation inhibited the cancer cell growth and metastasis associated with COX-2 and MMP-9 expression in MDA-MB‑231 human breast cancer cells, and that the antimetastatic effect of proton beam irradiation is achieved by the suppression of NF-κB phosphorylation via inhibition of Akt activation.
Therefore, not only Cox-2 but also EP1 and EP3 could be important targets for chemosensitization and inhibition of metastasis in breast cancers that are resistant to chemotherapy.