Blocking signaling through the gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity

Borsellino, Nicolò; Bonavida, Benjamin; Ciliberto, Gennaro; Toniatti, Carlo; Travali, Salvatore; D’Alessandro, Natale

doi:10.1002/(sici)1097-0142(19990101)85:1<134::aid-cncr19>3.0.co;2-c

Cited by 71 publications

(13 citation statements)

References 38 publications

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“…In prostate cancer, neutralization of endogenous IL-6 activity by an anti-IL-6 antibody, IL-6 antisense oligonucleotides or the receptor antagonist Sant7 was shown to increase sensitivity of PC3 and Du145 cells to induction of apoptosis by cytotoxic drugs (Borsellino et al, 1995(Borsellino et al, , 1999Pu et al, 2004). We found that LNCaP-IL-6 þ cells are more resistant than control cells to cytotoxicity of the calcium ionophore A23187.…”

Section: Discussionmentioning

confidence: 62%

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1

et al. 2006

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Section: Discussionmentioning

confidence: 62%

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1

et al. 2006

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“…Decreasing IL-6 levels in metastatic hormoneindependent prostate cancer cell lines by reducing nuclear factor nB signaling with an inhibitor of IKKh (PS-1145), a key pathway intermediate, increased their sensitivity to docetaxel (34). Similarly, Borsellino et al noted that inhibition of IL-6 signaling sensitized prostate cancer cells to etoposide and cisplatin (73). Future work in this area should continue to investigate the specificity of the two classes of inhibitors to tumor cells and their microenvironment to avoid possible toxicity.…”

Section: Preclinical Translational Advancesmentioning

confidence: 99%

The Bone Marrow Microenvironment as a Tumor Sanctuary and Contributor to Drug Resistance

Meads

Hazlehurst

Dalton

2008

Clinical Cancer Research

473

421

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The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of hematopoietic cells. These cells are supported by fibroblast-like bone marrow stromal cells, osteoblasts, and osteoclasts which secrete soluble factors and extracellular matrix proteins that mediate these functions. This rich environment serves as a safe haven not only for normal and malignant hematopoietic cells, but also for epithelial tumor cells that metastasize to bone, offering protection from chemotherapeutic agents by common mechanisms. Soluble factors produced in the bone marrow, such as stromal cell^derived factor-1 and interleukin-6, mediate homing, survival, and proliferation of tumor cells, and integrin-mediated adhesion sequesters tumor cells to this protective niche. Environment-mediated drug resistance includes a combination of soluble factors and adhesion, and can be subdivided into soluble factor^mediated drug resistance and cell adhesion^mediated drug resistance. Because it is induced immediately by the microenvironment and is independent of epigenetic or genetic changes caused by the selective pressure of drug exposure, environment-mediated drug resistance is a form of de novo drug resistance. In this form of drug resistance, tumor cells are transiently and reversibly protected from apoptosis induced by both chemotherapy and physiologic mediators of cell death. This protection allows tumor cells to survive the insult of chemotherapy, leading to minimal residual disease, and thereby increases the probability for the development of acquired drug resistance.

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“…133 Other IL-6 neutralizing agents have been studied in prostate cancer, including Sant7, which is a modified IL-6 molecule that binds the IL-6R subunit and blocks gp130 signaling while enhancing the sensitivity of the cells to etoposide and cisplatin. 134 Tkip, a novel tyrosine kinase inhibitor that is a peptide mimetic of SOCS1, inhibits proliferation of DU145 and LNCaP cell lines, possibly by blocking constitutive and IL-6-induced activation of STAT3, resulting in reduced levels of cyclin D1 and, thus, failure to enter the S-phase of the cell cycle. 135 …”

Section: Preclinical Studiesmentioning

confidence: 99%

Interleukin‐6 and its receptor in cancer

Hong

Angelo

Kurzrock

2007

Cancer

342

127

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Interleukin-6 (IL-6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL-6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL-6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL-6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL-6 are observed in almost every type of tumor studied and predict a poor outcome.

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Blocking signaling through the gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity

Cited by 71 publications

References 38 publications

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1

The Bone Marrow Microenvironment as a Tumor Sanctuary and Contributor to Drug Resistance

Interleukin‐6 and its receptor in cancer

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