Thus, immunohistochemical staining of leptin in colorectal cancer could be a helpful tool in the prediction of prognosis and survival pattern of colorectal cancer with certain clinicopathological factors (tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease).
Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay.
Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis.
We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients.
Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER⁺) breast cancer (BC) tumor growth and metastasis.
The expression of leptin and ObR was examined by immunohistochemistry in 148 primary breast cancers and 66 breast cancer metastases as well as in 90 benign mammary lesions.
Perturbations in the adipocytokine profile, especially higher levels of leptin, are a major cause of breast tumor progression and metastasis; the underlying mechanisms, however, are not well understood.
Furthermore, 5-FU combined with LEP-2a also resulted in p53 activation and NF-κB inhibition, and cell cycle arrest in the S phase as well as cell metastasis stagnation.
In the primary neoplasms and the metastatic nodes, expression of leptin correlated closely with leptin receptor (P < .001 for the primary neoplasms and P = .017 for nodal metastases).
Mechanistically, adipocyte-derived interleukin-6 (IL-6) and leptin may facilitate PLOD2 upregulation in breast cancer cells and promote breast cancer metastasis in tail vein metastasis assays.
This review also addresses leptin's metabolic interactions with cytokines, growth factors or hormones, establishing perceptive pathways leading to carcinogenesis or prostate cancer progression and metastasis.
Given the important role of leptin in breast cancer growth and metastasis, novel strategies to antagonize biological effects of this adipocytokine are much desired.
In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.
Indeed, pathological remodelling of white adipose tissue and increased levels of fat-specific cytokines (mainly leptin), as a consequence of the obesity condition, have been associated with several hallmarks of breast cancer, such as sustained proliferative signaling, cellular energetics, inflammation, angiogenesis, activating invasion and metastasis.