Assessment and Prognosis of Prostate Cancer Metastasis

 

Prostate cancer is the second leading cause of malignancy-related mortality in males. Prostate cancer cells spread to liver, lungs, and especially bone via the blood stream and form secondary tumors in these organs. Bone metastases are incurable and a major complication of prostate cancer patients. Cancer cell motility towards increasing concentrations of certain chemicals plays an important role in metastases. Several chemicals such as chemokines and growth factors are believed to influence the migration of prostate cancer cells. Despite improvement in clinical response rates with newly developed targeted multi-kinase inhibitors, death due to metastases remain major impediments to its cure. With a focus on the development of new inhibitors, particularly, RLIP76 blockade has been shown highly effective. The findings are potentially of major clinical significance because they promise a unique, highly effective and functionally cancer-specific targeted therapy. 

However, limitation of available tools has resulted in inadequate knowledge about the dynamic effects of the chemical gradients on prostate cancer migration and related proteomic mechanisms at the cellular level responsible for metastasis. In this collaborated project, we have developed a novel assay that integrates the microfluidic cell migration platform and ultra sensitive silicon nanowires field-effect transistor biomarker sensors to study cancer cell migration associated with prostate cancer metastasis. The high-throughput arrayed microfluidic assays have been demonstrated for feasibility, and utilized for studying prostate cancer cell migration dynamics in our experiments. The devices have a capacity of assaying individual chemokines and their combinations, with and without the knockdown of RLIP76, in a parallel and time-lapsed fashion. Both mesangial and cancer cells were tested. Four markers were tested in multiple experiments and the effects were found as: HNE (mesangial: attract, cancer: inhibit), GSHNE (mesangial: attract, cancer: attract), IL-7 (mesangial: inhibit, cancer: inhibit), anti-RLIP76 (mesangial: inhibit, cancer: inhibit). The data gathered can provide important information in designing anti-metastasis drugs. More importantly, our devices are proven to have ability to assay the metastatic markers and provide time-lapsed information of prostate cancer cell migration.  The devices can be used in many applications to assay the cellular and molecular responses in cell migration.  

Publications, Patents filed, additional funding secured for each project

  • , W. Hu, Applied Physics Letters, Volume 100, Issue 15, Article Number: 153502, 2012.
  • “Performance Analysis of Si Nanowire Biosensor By Numerical modeling for Charge Sensing, ” X. Yang, W. Frensley, D. Zhou, and W. Hu, IEEE Trans. Nanotech., 11(3), pp.501-512, 2012.
  • “Ultrasensitive protein detection using lithographically defined Si multinanowire field effect transistors,” R. Tian, S. Regonda, J. Gao, Y. Liu, and W. Hu, Lab Chip 11, pp.1952-1961, 2011.
  • “Demonstration of Cancer Cell Migration Using a Novel Microfluidic Device,” S. M. N. Rao, V. K. Lin, U. Tata, G. V. Raj, J.-T. Hsieh, K. Nguyen, and J.-C. Chiao, Journal of Nanotechnology in Engineering and Medicine, Vol. 1, No.2, May 2010.
  •  “Molecular Characterization of Epithelial to Mesenchymal Transition in Human Prostatic Epithelial Cells,” V. K. Lin , S.-Y. Wang, L. Wu, S. M. Rao, J. -C. Chiao, C. G. Roehrborn, Journal of Nanotechnology in Engineering and Medicine, Vol. 1, No.2, May 2010.
  • “Preliminary Characterization of a Novel Microfluidic Device to Evaluate Prostate Cancer Cell Migration,” S. Rao, K. Hardy, V. Lin, J.-C. Chiao, G. Raj, The Journal of Urology, Vol. 183, No. 4, pp. e93-94, May 30, 2010.
  •  “Study of Prostate Cancer Cell Line PC3-ML Chemotaxsis to Epidermal Growth Factor with a BIOMEMS Device,” U. Tata, S. M.N Rao, A. Sharma, K. Pabba, K. Pokhrel, V. K. Lin, H. Cao, and J.-C. Chiao, International Workshop on Nanotechnology and Application, IWNA2011, Nov. 10-12 2011.
  • “Microfluidic Assay for Metastasis Potential Analysis,” S. M. N. Rao, U. Tata, V. Lin, J.-T. Hsieh, K. Nguyen, J.-C. Chiao, ASME Global Congress on Nanoengineering for Medicine and Biology, NEMB2010, Houston, TX, February 7-10, 2010. Full paper.
  • “Migration Characteristics of Prostate Cancer Cells in Response to Epidermal Growth Factor (EGF),” S. Rao, U. Tata, K. C. Pabba, K. Pokhrel, A. Sharma, V. Lin, and J-C. Chiao, BMES Biomedical Engineering Society Annual Meeting, Hartford, Oct. 12-15, 2011.
  • “A Microfluidic Approach to Study the Effect of Growth Factors on PC3 Cell Migration,” U. Tata, S. Rao, K. T. Nguyen, V. K. Lin, and J-C. Chiao, BMES Biomedical Engineering Society Annual Meeting, Hartford, Oct. 12-15, 2011.
  • “A Study for the Prostate Cancer Cell Migration toward Epidermal Growth Factor (EGF), ” K. C. Pabba, K. Pokhrel, A. Sharma, U. Tata, S. Rao, V. Lin, J.-C. Chiao, The 27th Southern Biomedical Engineering Conference, Arlington, TX, April 30-May 1, 2011.
  • “Demonstration of EMT in prostate Cancer Cells Migrating in Response to TGF-beta,” S. Rao, U. Tata, V. Lin, J.-C. Chiao, The 27th Southern Biomedical Engineering Conference, Arlington, TX, April 30-May 1, 2011.
  • “A Microfluidic Assay to Study the Effect of Growth Factors on PC3 Cell Migration,” U. Tata, S. M. N. Rao, K. Nguyen, V. K. Lin and J.-C. Chiao, The 27th Southern Biomedical Engineering Conference, Arlington, TX, April 30, 2011.
  • “Migration of PC-3 cells Under the Influence of Various EGF Concentrations,” S. Salodkar1, U. Tata, S. Rao, K. T. Nguyen and J.-C. Chiao, BMES Biomedical Engineering Society Annual Fall Scientific Meeting, Austin, TX, October 6 – 9, 2010.
  • “The Effects of RLIP76 on the Migration of CaKi-2 and HMC Cells in Response to HNE and HNESG,” S. Rao, U. Tata, P. Singhal, S. Singhal, S. Awasthi, K.T. Nguyen and J.-C. Chiao, BMES Biomedical Engineering Society Annual Fall Scientific Meeting, Austin, TX, October 6 – 9, 2010.
  • “Effects of EGF on the migration of prostate cancer cell line PC3-ML,” U. Tata, S. M. N. Rao, K. Nguyen, and J-C. Chiao, BMES Biomedical Engineering Society Annual Fall Scientific Meeting, Austin, TX, October 6 – 9, 2010.
  • An IP was disclosed to UTA Technology Transfer Office on Sept. 3 2009
  • Two IPs were disclosed to UTD Technology Transfer Office. 2010 and 2012.

 

“The TexasMRC grant allows us to conduct initial tests and build a prototype for preliminary data before we can implement full-scale statistically meaningful experiments. The grant mechanism helps us to integrate complementary collaborators in a synergistic team to accomplish significant works.”

Primary Investigators:

J.C. Chiao (UTA)
Walter Hu (UTD)
Sanjay Awasthi (THR)
Jingming Gao (UTD)

 

Leave a Comment About This Project

Your email address will not be published.

Please Prove You Are Human *

Ilo6M