alexa Gather Round: In vitro tumor spheroids as improved models of in vivo tumors | OMICS International
ISSN: 2155-9538
Journal of Bioengineering & Biomedical Science

Like us on:

Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Gather Round: In vitro tumor spheroids as improved models of in vivo tumors

Siddarth Chandrasekaran and Michael R. King*

Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA

*Corresponding Author:
Michael R. King
Department of Biomedical Engineering
Cornell University, Ithaca
New York, USA
E-mail: [email protected]

Received Date: October 22, 2012; Accepted Date: October 23, 2012; Published Date: October 25, 2012

Citation: Chandrasekaran S, King MR (2012) Gather Round: In Vitro Tumor Spheroids as Improved Models of In Vivo Tumors. J Bioengineer & Biomedical Sci 2: e109. doi: 10.4172/2155-9538.1000e109

Copyright: © 2012 Chandrasekaran S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Bioengineering & Biomedical Science

Continued efforts to understand cancer have progressed in parallel with tendencies of tumors to evade conventional treatments used to control tumor progression. Cancer cells fit the ‘survival of the fittest’ paradigm given the fact that they exist in an aberrant in vivo environment consisting of compromised blood supply, low oxygen concentration, large amounts of reducing equivalents, low pH and hypoxia to name a few [1]. This differs from the normal tissue environment, where a perfect homeostasis is maintained. These in vivo pathophysiological gradients play an important role in tumor progression and their response to treatment [2]. To illustrate this idea, we describe two of many examples where these gradients play an important role in determining the molecular basis of biological incongruities found in tumors. For instance, hypoxic conditions can make cells resistant to radio-ablative therapy because radiotherapy relies on DNA damage orchestrated by oxygen centered free radicals [3]. The gradient in glucose results in a gradient in cellular proliferation, resulting in a slower dividing cell population in the center of the tumor giving rise to cancer stem cells [4]. Thus, asking important questions about tumor progression and efficacy to drugs on cancer cells cultured as a conventional monolayer has little physiological relevance. Cancer cells cultured as 3D spheroids have brought cancer research a step closer to in vivo tumors by recreating the physiologically relevant gradients of factors such as nutrients, oxygen, pH and cellular proliferation (Figure 1). The past decade has seen several approaches for culturing cells as multicellular spheroids in which microfabrication and biomaterials have played important roles in facilitating new insights.


Figure 1: Pathophysiological gradients in a 3D tumor spheroid.

The most popular method for spheroid cell culture is the hanging drop technique where cells are grown in small droplets on an inverted surface [5]. However, the small media volume for so many cells in a 10-20 μL droplet is a significant disadvantage of this method. Microfabrication has played an important role in developing 3D cell culture platforms for cancer research [6]. The advantages of microfabrication include high fidelity molding of micron-size surface topographies, chemical modification of the surface, and potential integration into microfluidic devices. Our group has developed a gas expansion molding (GEM) technique for generating microbubbles which are 80-150 μm diameter spherical compartments formed on polydimethylsiloxane (PDMS), a silicone based elastomeric polymer. We showed that arrays of spherical cavities formed on PDMS [7] using this technique can be used for culturing cancer cells as spheroids [8]. The unique geometry of microbubbles allows the cells to rapidly condition their microenvironment by secreting soluble factors to influence their function [9]. Also, perfusion culture system using microbubble arrays has shown that Colo205 cells cultured as spheroids under flow are more resistant to doxorubicin treatment resembling the actual disease condition [10].

Despite the obvious advantages of microfabricated cell culture platforms such as high-throughput design and easy integration with microfluidic systems, the size of spheroids that can be generated by these techniques is often limited by the geometry of the cell culture platform. The maximum number of cells that can be seeded onto microfabricated wells is often less than 103. To mimic the primary tumor before vascularization the number of cells in a tumor spheroid should be more than a few thousand and size should be 400-600 μm in diameter [11], something that cannot be easily achieved by microfabricated cell culture platforms. An alternative approach to generate tumor spheroids to mimic a primary tumor is to culture them in rotating wall vessel bioreactors for an extended period of time upto 16 days [12]. While this method has been quite successful in generating spheroids of increased size, the time frame and equipment cost remain limiting factors. The use of biocompatible polymers for spheroid cell culture has been popular since 1970s. In fact, the very first method for propagating cancer cells as multicellular aggregates involved culturing them on agar [13]. Hydrophobic polymers hinder cells from adhering to the substrate, resulting in increased cell-cell interaction and enabling their propagation as spheroids. We showed that WM115, a metastatic melanoma cell line cultured on a PDMS showed altered spheroid morphology with increased presence of cells expressing stem-cell markers when compared to cells propagating as a monolayer [14]. Breast cancer cells propagating as 3D spheroids on PDMS showed increased expression of E-selectin ligands and had a significantly stronger interaction with human recombinant E-selectin when compared to monolayer cells [15]. This supports the idea that studying important aspects of tumor progression makes a significant difference when cancer cell lines are cultured as tumor spheroids.

While monoculture of tumor spheroids have been of importance, spheroid co-culture is a tool that is gaining increased attention in cancer research. Tumors in vivo are vastly heterogeneous, consisting of cancer cells with different levels of aggressiveness with infiltrating endothelial cells, cancer associated fibroblasts and macrophages [16]. Heterogeneity results from heterotypic interactions that are believed to play a role in deciding the ability of a cell to metastasize from the primary site. This heterogeneity could be partly captured in vitro by co-culturing cell lines with different metastatic potential. Co-culturing non-tumorigenic mammary epithelial cell line MCF10A, with the weakly metastatic MCF7 cell line and the highly metastatic BT20 cell line as 3D spheroids resulted in favoring the E-selectin mediated adhesion of the highly metastatic BT20 cell line [15]. The co-culture conditions also increased the invasiveness of the most aggressive cell subpopulation. Thus, co-culture tumor spheroids can closely mimic the in vivo homotypic and heterotypic interactions offering a platform for addressing important questions about cancer metastasis in physiologically relevant scenarios.

In summary, spheroid monoculture and co-culture could potentially replace conventional monolayer culture in cancer research. Though cancer cell lines offer several advantages such as ease in handling, unlimited passages in vitro and considerable heterogeneity; all of these advantages risk being lost when cultured as a 2D monolayer. The advent of microfabrication and biomaterials have paved the way for 3D culture of cancer cells which offers all these advantages in an in vivo-like environment recreating a cellular microenvironment with cell-cell homotypic and heterotypic interactions.


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 12941
  • [From(publication date):
    December-2012 - Jul 23, 2018]
  • Breakdown by view type
  • HTML page views : 9061
  • PDF downloads : 3880

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

+1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals


[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7