Conor Lynch, PhD

The goal of our laboratory is to understand how metastatic prostate cancer cells interact with the bone microenvironment to establish and grow as secondary cancers using in vivo and in vitro techniques. The lab has made major inroads into defining how matrix metalloproteinases (MMPs) contribute the prostate cancer progression in bone.

• Thiolloy S, Edwards JR, Fingleton B, Rifkin DB, Matrisian LM, Lynch CC. An osteoblast-derived proteinase controls tumor cell survival via TGF-beta activation in the bone microenvironment. PLoS One. 2012;7(1):e29862. Pubmedid: 22238668. Pmcid: PMC3251607.
• Shah M, Huang D, Blick T, Connor A, Reiter LA, Hardink JR, Lynch CC, Waltham M, Thompson EW. An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer. PLoS One. 2012;7(1):e29615. Pubmedid: 22253746. Pmcid: PMC3256168.
• Halpern JL, Kilbarger A, Lynch CC. Mesenchymal stem cells promote mammary cancer cell migration in vitro via the CXCR2 receptor. Cancer Lett. 2011 Sep;308(1):91-99. Pubmedid: 21601983. Pmcid: PMC3311035.
• Nyman JS, Lynch CC, Perrien DS, Thiolloy S, O'Quinn EC, Patil CA, Bi X, Pharr GM, Mahadevan-Jansen A, Mundy GR. Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone. J Bone Miner Res. 2011 Jun;26(6):1252-1260. Pubmedid: 21611966. Pmcid: PMC3312757.
• Bi X, Patil CA, Lynch CC, Pharr GM, Mahadevan-Jansen A, Nyman JS. Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse model. J Biomech. 2011 Jan;44(2):297-303. Pubmedid: 21035119. Pmcid: PMC3019269.
• Lynch CC. Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone. 2011 Jan;48(1):44-53. Pubmedid: 20601294.
• Nyman JS, Lynch CC, Perrien DS, Thiolloy S, O'Quinn EC, Patil CA, Bi X, Pharr GM, Mahadevan-Jansen A, Mundy GR. Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone. J Bone Miner Res. 2010 Dec. Pubmedid: 21191960.
• Lynch CC, Vargo-Gogola T, Matrisian LM, Fingleton B. Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA. J Oncol. 2010 Jun;2010:530745. Pubmedid: 20628524. Pmcid: PMC2902104.
• Bruni-Cardoso A, Johnson LC, Vessella RL, Peterson TE, Lynch CC. Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment. Mol Cancer Res. 2010 Apr;8(4):459-470. Pubmedid: 20332212. Pmcid: PMC2946627.
• Min Y, Ren X, Vaught DB, Chen J, Donnelly E, Lynch CC, Lin PC. Tie2 signaling regulates osteoclastogenesis and osteolytic bone invasion of breast cancer. Cancer Res. 2010 Apr;70(7):2819-2828. Pubmedid: 20233869. Pmcid: PMC2848896.
• Schoenecker J, Mignemi N, Stutz C, Liu Q, Edwards J, Lynch C, Holt G, Schwartz H, Mencio G, Hamm H. 2010 Young Investigator Award winner: Therapeutic aprotinin stimulates osteoblast proliferation but inhibits differentiation and bone matrix mineralization. Spine (Phila Pa 1976). 2010 Apr;35(9):1008-1016. Pubmedid: 20407341.
• Fingleton B, Lynch CC. A new dress code for MMPs: cleavage optional. Dev Cell. 2010 Jan;18(1):3-4. Pubmedid: 20152171.
• Fowler JA, Mundy GR, Lwin ST, Lynch CC, Edwards CM. A murine model of myeloma that allows genetic manipulation of the host microenvironment. Dis Model Mech. 2009 Nov;2(11-12):604-611. Pubmedid: 19779066. Pmcid: PMC2776114.
• Thiolloy S, Halpern J, Holt GE, Schwartz HS, Mundy GR, Matrisian LM, Lynch CC. Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysis. Cancer Res. 2009 Aug;69(16):6747-6755. Pubmedid: 19679556. Pmcid: PMC2745595.
• Welch DR, Cooper CR, Hurst DR, Lynch CC, Martin MD, Vaidya KS, VanSaun MN, Mastro AM. Metastasis Research Society-American Association For Cancer Research Joint Conference on Metastasis. Cancer Res. 2008 Dec;68(23):9578-9582. Pubmedid: 19047132. Pmcid: PMC2741417.
• Holt GE, Halpern JL, Lynch CC, Devin CJ, Schwartz HS. Imaging analysis of the in vivo bioreactor: a preliminary study. Clin Orthop Relat Res. 2008 Aug;466(8):1890-1896. Pubmedid: 18506563. Pmcid: PMC2584254.
• Martin MD, Carter KJ, Jean-Philippe SR, Chang M, Mobashery S, Thiolloy S, Lynch CC, Matrisian LM, Fingleton B. Effect of ablation or inhibition of stromal matrix metalloproteinase-9 on lung metastasis in a breast cancer model is dependent on genetic background. Cancer Res. 2008 Aug;68(15):6251-6259. Pubmedid: 18676849. Pmcid: PMC2789265.
• Martin MD, Fingleton B, Lynch CC, Wells S, McIntyre JO, Piston DW, Matrisian LM. Establishment and quantitative imaging of a 3D lung organotypic model of mammary tumor outgrowth. Clin Exp Metastasis. 2008;25(8):877-885. Pubmedid: 18787962. Pmcid: PMC2588650.
• Lynch CC, Vargo-Gogola T, Martin MD, Fingleton B, Crawford HC, Matrisian LM. Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor. Cancer Res. 2007 Jul;67(14):6760-6767. Pubmedid: 17638887.
• Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK, Vargo-Gogola TC, Begtrup JL, Peterson TE, Fingleton B, Shirai T, Matrisian LM, Futakuchi M. MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell. 2005 May;7(5):485-496. Pubmedid: 15894268.
• Lynch CC, Crawford HC, Matrisian LM, McDonnell S. Epidermal growth factor upregulates matrix metalloproteinase-7 expression through activation of PEA3 transcription factors. Int J Oncol. 2004 Jun;24(6):1565-1572. Pubmedid: 15138601.
• McIntyre JO, Fingleton B, Wells KS, Piston DW, Lynch CC, Gautam S, Matrisian LM. Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochem J. 2004 Feb;377(Pt 3):617-628. Pubmedid: 14556651. Pmcid: PMC1223892.
• Lynch CC, Matrisian LM. Matrix metalloproteinases in tumor-host cell communication. Differentiation. 2002 Dec;70(9-10):561-573. Pubmedid: 12492497.
• Harmey JH, Bucana CD, Lu W, Byrne AM, McDonnell S, Lynch C, Bouchier-Hayes D, Dong Z. Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. Int J Cancer. 2002 Oct;101(5):415-422. Pubmedid: 12216068.
• Lynch CC, McDonnell S. The role of matrilysin (MMP-7) in leukaemia cell invasion. Clin Exp Metastasis. 2000;18(5):401-406. Pubmedid: 11467772.
• McDonnell S, Morgan M, Lynch C. Role of matrix metalloproteinases in normal and disease processes. Biochem Soc Trans. 1999 Aug;27(4):734-740. Pubmedid: 10917674.