Department of Pathology, Microbiology, and Immunology


  Shanna A. Arnold, Ph.D., M.S.C.I. 



Research Instructor

Dept. of Pathology, Microbiology and Immunology


  Contact Information



Office Location:

MCN C-2103

Phone: 615-343-1205

E-mail:  shanna.arnold@vanderbilt.edu

Campus Mail Address:

Pathology, Microbiology and Immunology-3rd Fl

MCN C-3321 (2561)


Mailing Address:

Vanderbilt University School of Medicine

Pathology, Microbiology and Immunology-3rd Fl 

MCN C-3321

Nashville, TN 37232-2561



Research Keywords



Cancer, Extracellular Matrix, Biomarker, Angiogenesis, Cell Adhesion, Translational Research, Metastasis, Cell Migration



Research Description



It is estimated that there will be 140,430 new diagnoses of urogenital cancers and 30,000 associated deaths in 2013. Metastatic progression is the primary cause of cancer-related death. Managing care for cancer patients with progressive disease is an arduous challenge and poses an increasing financial burden on our medical institutions. Therefore, is imperative that we elucidate the molecular mechanisms that drive metastasis and identify clinical biomarkers that can specifically recognize invasive disease and rapidly assess therapeutic response. Our objective is to discover and validate fluid-based biomarkers for disease surveillance, monitoring treatment response, and predicting recurrence. Furthermore, we aim to determine the mechanisms underlying these biomarkers that drive tumor cell survival and migration.

We have identified Activated Leukocyte Cell Adhesion Molecule (ALCAM) as an important regulator of tumor cell motility and metastasis in both pre-clinical and mechanistic studies. We have demonstrated that ALCAM is a critical contributor to tumor cell metastasis. By analyzing ALCAM in the serum of tumor-bearing animals, we demonstrated that shedding of the extracellular domain of ALCAM corresponds to disease progression and tumor burden. Furthermore, we found significantly elevated ALCAM levels in both the urine and serum of patients with renal (RCC) and bladder (BCa) cancer. Based on our preliminary studies, we hypothesize that the proteolytic shedding of ALCAM contributes to disease progression and that shed ALCAM is a biomarker of disease progression, as well as treatment response in urogenital cancers. The value of shed ALCAM as a biomarker is two-fold: 1) It is a mechanistic link to tumor cell migration and, subsequently, able to report on invasive disease rather than merely the presence of cancer, and 2) The non-invasive detection of ALCAM in urine and serum offers longitudinal assessment of treatment response and disease progression. In addition, understanding how proteolytic processing of ALCAM contributes mechanistically to disease progression will reveal therapeutic approaches that can intervene in the malignant dissemination of cancer.

Our research plan has three aspects that include validating ALCAM as a biomarker in urogenital cancers, determining the function of various ALCAM domains in tumor cell survival and metastasis, and discovering new biomarkers similar to ALCAM in function and utility.

The clinical impact of such biomarkers would be multifaceted by reducing healthcare costs, reducing toxicities associated with ineffective drugs, and improving the implementation of drug trials. In summary, successful implementation of active monitoring for recurrence and rapid identification of treatment response is synonymous with reducing morbidity, mortality, and the associated cost of health care.






Palmer, TD, Mart??nez, CH, Vasquez, C, Hebron, KE, Jones-Paris, C, Arnold, SA, Chan, SM, Chalasani, V, Gomez-Lemus, JA, Williams, AK, Chin, JL, Giannico, GA, Ketova, T, Lewis, JD, Zijlstra, A. Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. Cancer Res, 74(1), 173-87, 2014

Hansen, AG, Arnold, SA, Jiang, M, Palmer, TD, Ketova, T, Merkel, A, Pickup, M, Samaras, S, Shyr, Y, Moses, HL, Hayward, SW, Sterling, JA, Zijlstra, A. ALCAM/CD166 is a TGF-??-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res, 74(5), 1404-15, 2014

Hansen, AG, Freeman, TJ, Arnold, SA, Starchenko, A, Jones-Paris, CR, Gilger, MA, Washington, MK, Fan, KH, Shyr, Y, Beauchamp, RD, Zijlstra, A. Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Cancer Res, 73(10), 2955-64, 2013

Arnold, SA, Rivera, LB, Carbon, JG, Toombs, JE, Chang, CL, Bradshaw, AD, Brekken, RA. Losartan slows pancreatic tumor progression and extends survival of SPARC-null mice by abrogating aberrant TGF?? activation. PLoS One, 7(2), e31384, 2012

Arnold, SA, Brekken, RA. SPARC: a matricellular regulator of tumorigenesis. J Cell Commun Signal, 3(3-4), 255-73, 2009

Arnold, SA, Rivera, LB, Miller, AF, Carbon, JG, Dineen, SP, Xie, Y, Castrillon, DH, Sage, EH, Puolakkainen, P, Bradshaw, AD, Brekken, RA. Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma. Dis Model Mech, 3(1-2), 57-72, 2009

Bull Phelps, SL, Carbon, J, Miller, A, Castro-Rivera, E, Arnold, S, Brekken, RA, Lea, JS. Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity. Am J Obstet Gynecol, 200(2), 180.e1-7, 2009

Arnold, S, Mira, E, Muneer, S, Korpanty, G, Beck, AW, Holloway, SE, Ma??es, S, Brekken, RA. Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. Exp Biol Med (Maywood), 233(7), 860-73, 2008