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    Christopher Louis Hall PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
        Overview 
        Narrative

        Integrin Biology in Prostate Cancer Skeletal Metastasis

        Prostate cancer (PCa) is a significant health problem among men in the United States.  In 2013, PCa is expected to be the most frequently diagnosed cancer in men and the second leading cause of cancer-related deaths within this group.  Of the 28,000 estimated deaths attributable to PCa this year, all will follow the metastatic spread of the disease from the prostate to distant organs including the dura, liver, lung, and skeleton.  The most frequent distant metastases formed by malignant PCa are within the skeleton.  Studies of men with progressive castration-resistant PCa indicate that nearly one half of patients will develop skeletal metastases within two years; whereas, at autopsy greater than 80% of all men who die of PCa will have metastatic disease within the bone, specifically in the trabecular bone of the pelvis, femur, and vertebral bodies.  Outgrowth of tumors within the bone is quite debilitating resulting in severe pain, fracture, nerve compression/paralysis, and death. Thus to improve the quality of life for PCa patients, a better understanding of the biology of skeletal metastases is needed. 

        The goal of my research program is to define the mechanism through which PCa cells preferentially metastasize to the skeleton.  Recent data suggest that the colonization of the skeleton is mediated in part by collagen type I, the most abundant protein within the bone.  We have shown that enhanced binding to collagen I through increased expression of integrin a2b1 stimulated in vitro invasion and promoted the growth of PCa cells within the bone.  We have further shown that the invasive phenotype of collagen I-binding PCa cells is mediated in part by the a2b1-dependent activation of RhoC GTPase.  The selective knock-down of a2b1 integrin was found to reduce both RhoC activity and the experimental metastasis of PCa cells to the bone confirming that a2b1 integrin promotes PCa skeletal metastasis.  Current studies are focused on identifying the molecular mechanism of a2b1-mediated RhoC activation as well as defining the role of collagen I/a2b1 integrin in the transition from cellular dormancy to metastatic growth within disseminated PCa cells.

        Academic Background

        Ph. D., The University of Texas Health Science Center at Houston, 2001



        Bibliographic 
        selected publications
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        1. Ithimakin S, Day KC, Malik F, Zen Q, Dawsey SJ, Bersano-Begey TF, Quraishi AA, Ignatoski KW, Daignault S, Davis A, Hall CL, Palanisamy N, Heath AN, Tawakkol N, Luther TK, Clouthier SG, Chadwick WA, Day ML, Kleer CG, Thomas DG, Hayes DF, Korkaya H, Wicha MS. HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab. Cancer Res. 2013 Mar 1; 73(5):1635-46.
          View in: PubMed
        2. Sottnik JL, Daignault-Newton S, Zhang X, Morrissey C, Hussain MH, Keller ET, Hall CL. Integrin alpha(2)beta (1) (a (2)ß (1)) promotes prostate cancer skeletal metastasis. Clin Exp Metastasis. 2012 Dec 15.
          View in: PubMed
        3. Sottnik JL, Hall CL, Zhang J, Keller ET. Wnt and Wnt inhibitors in bone metastasis. Bonekey Rep. 2012; 1:101.
          View in: PubMed
        4. Hall CL, Zhang H, Baile S, Ljungman M, Kuhstoss S, Keller ET. p21CIP-1/WAF-1 induction is required to inhibit prostate cancer growth elicited by deficient expression of the Wnt inhibitor Dickkopf-1. Cancer Res. 2010 Dec 1; 70(23):9916-26.
          View in: PubMed
        5. Jung Y, Shiozawa Y, Wang J, Wang J, Wang Z, Pedersen EA, Lee CH, Hall CL, Hogg PJ, Krebsbach PH, Keller ET, Taichman RS. Expression of PGK1 by prostate cancer cells induces bone formation. Mol Cancer Res. 2009 Oct; 7(10):1595-604.
          View in: PubMed
        6. Kasina S, Scherle PA, Hall CL, Macoska JA. ADAM-mediated amphiregulin shedding and EGFR transactivation. Cell Prolif. 2009 Dec; 42(6):799-812.
          View in: PubMed
        7. Comstock KE, Hall CL, Daignault S, Mandlebaum SA, Yu C, Keller ET. A bioluminescent orthotopic mouse model of human osteosarcoma that allows sensitive and rapid evaluation of new therapeutic agents In vivo. In Vivo. 2009 Sep-Oct; 23(5):661-8.
          View in: PubMed
        8. Hall CL, Daignault SD, Shah RB, Pienta KJ, Keller ET. Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis. Prostate. 2008 Sep 15; 68(13):1396-404.
          View in: PubMed
        9. Bu G, Lu W, Liu CC, Selander K, Yoneda T, Hall C, Keller ET, Li Y. Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: implication for breast cancer osteolytic bone metastases. Int J Cancer. 2008 Sep 1; 123(5):1034-42.
          View in: PubMed
        10. Hall CL, Dubyk CW, Riesenberger TA, Shein D, Keller ET, van Golen KL. Type I collagen receptor (alpha2beta1) signaling promotes prostate cancer invasion through RhoC GTPase. Neoplasia. 2008 Aug; 10(8):797-803.
          View in: PubMed
        11. Dai J, Hall CL, Escara-Wilke J, Mizokami A, Keller JM, Keller ET. Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Res. 2008 Jul 15; 68(14):5785-94.
          View in: PubMed
        12. Keller ET, Dai J, Escara-Wilke J, Hall CL, Ignatoski K, Taichman RS, Keller J. New trends in the treatment of bone metastasis. J Cell Biochem. 2007 Dec 1; 102(5):1095-102.
          View in: PubMed
        13. Hall CL, Keller ET. The role of Wnts in bone metastases. Cancer Metastasis Rev. 2006 Dec; 25(4):551-8.
          View in: PubMed
        14. Hall CL, Dai J, van Golen KL, Keller ET, Long MW. Type I collagen receptor (alpha 2 beta 1) signaling promotes the growth of human prostate cancer cells within the bone. Cancer Res. 2006 Sep 1; 66(17):8648-54.
          View in: PubMed
        15. Hall CL, Kang S, MacDougald OA, Keller ET. Role of Wnts in prostate cancer bone metastases. J Cell Biochem. 2006 Mar 1; 97(4):661-72.
          View in: PubMed
        16. Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET. Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res. 2005 Sep 1; 65(17):7554-60.
          View in: PubMed
        17. Hall CL, Tsan R, Mugnai G, Mazar A, Radinsky R, Pettaway CA. Enhanced invasion of hormone refractory prostate cancer cells through hepatocyte growth factor (HGF) induction of urokinase-type plasminogen activator (u-PA). Prostate. 2004 May 1; 59(2):167-76.
          View in: PubMed
        18. Hall CL, Yao M, Hill LL, Owen-Schaub LB. Essential role for hematopoietic Fas ligand (FasL) in the suppression of melanoma lung metastasis revealed in bone marrow chimeric mice. Clin Exp Metastasis. 2004; 21(3):251-6.
          View in: PubMed
        19. Weaver T, Hall CL, Kachel DL, Ward RP, Williams MD, Perry DG, Wisniowski P, Martin WJ. Assessment of in vivo attachment/phagocytosis by alveolar macrophages. J Immunol Methods. 1996 Jun 21; 193(2):149-56.
          View in: PubMed
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