Because IL-6 belongs to the hematopoietic cytokine family, which includes leukemia inhibitory factor (LIF) and interleukin-11 (IL-11), we examined the possibility of coordinate expression of LIF, IL-6, and IL-11 in three human melanoma cell lines derived from primary lesions (early) and in four lines derived from metastatic tumors (advanced).
Next, two IL-6-producing melanoma cell lines, both of which were derived from metastases, MeWo and WM9, and which are growth resistant to exogenously added IL-6, were transfected with an antisense IL-6 expression vector.
The authors therefore implicate IL-6 as a possible factor important in breast cancer progression and metastasis formation, although the clinical significance of this cytokine in breast cancer patients could not be established.
Experimental data suggest that interleukin 6 (IL-6) plays an important role in the development and progression of metastasis from colorectal cancer (CRC), and -174 G>C polymorphism has been identified recently in the IL-6 gene promoter.
For patients undergoing radical prostatectomy, preoperative plasma levels of TGF-beta(1) and IL-6sR are associated with metastases to regional lymph nodes, presumed occult metastases at the time of primary treatment, and disease progression.
These findings suggested that the expression of VEGF-A, C and their regulation by IL-1alpha, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.
Moreover, stromal and immunological cells and their cytokines coordinate critical pathways that exert important roles in the ability of tumors to invade and metastasize, thus suppressive cytokines (IL-6 and IL-10) and neutralizing specific antibodies might subvert conditions for metastasis.
Our data are in support of an association between elevated relative microvessel area of the primary tumour and the presence of bone marrow micrometastases in breast cancer patients with operable disease, and corroborate the paracrine and endocrine role of interleukin-6 and the involvement of coagulation in breast cancer growth and metastasis.
Differential baseline and response profile to IFN-gamma gene transduction of IL-6/IL-6 receptor-alpha secretion discriminate primary tumors versus bone marrow metastases of nasopharyngeal carcinomas in culture.
To test the hypothesis that tumor-associated macrophages (TAMs) enhance the growth and metastasis of human prostate cancer in the bone, we evaluated the effects of decreasing interleukin-6 (IL-6) production by tumor cells and TAMs in a mouse model of bone metastasis.
Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels.
Biologically, this resulted in a consequential impairment of protumorigenic myeloid-derived suppressor cells (MDSC), as restoration of IL-6 recovered both MDSC suppressor function and metastasis susceptibility in Ido1-nullizygous mice.
Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signaling.