# Tumour spheroid models (hanging-drop and ultra-low-attachment culture)

Source: https://onco.cc/technologies/tumour-spheroid-models/  
OnCo record `tumour-spheroid-models` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Instead of growing cancer cells flat on plastic, they are grown as small balls of a few thousand cells. The balls develop an outer layer of dividing cells and a starved centre, much like a small tumour nodule, which makes them a better test of how drugs get in and act.

## Summary

Sutherland, McCredie and Inch described multicell spheroids as a model of nodular carcinoma in 1971. Spheroids form when cells are prevented from attaching to a surface, so they aggregate and grow in three dimensions, building oxygen, nutrient and proliferation gradients with a necrotic core once they pass a few hundred micrometres. Kelm and colleagues (2003) described the hanging-drop method, in which each spheroid forms in a drop suspended from a microtitre plate: it worked across a broad range of cell lines with nearly one spheroid per drop and a narrow size distribution (coefficient of variation 10 to 15 per cent, against 40 to 60 per cent for growth on non-adherent surfaces). Plates with ultra-low-attachment surfaces and round-bottomed wells are the other common format, and both are used for high-throughput drug screening.

Spheroids sit between flat cell culture and organoids: they are made from cell lines or primary cells rather than stem-cell-derived tissue, and are cheaper and more uniform, but they do not reproduce the architecture of the tumour they came from.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-11-03
- Also known as: multicellular tumour spheroids; multicellular tumor spheroids; MCTS; spheroid models; hanging-drop spheroids; ultra-low-attachment spheroids; 3D spheroid culture
- Principle: Cells kept from adhering to a surface aggregate into a three-dimensional sphere whose size sets diffusion gradients of oxygen, nutrients and drugs, giving proliferating, quiescent and necrotic zones.
- Since: 1971
- Strengths: Reproduce diffusion gradients and a hypoxic core; Uniform, cheap and suited to screening plates; Better predictor of drug penetration than flat culture
- Limitations: Usually lack immune cells, stroma and vessels unless added; Cell-line spheroids do not reproduce tumour architecture; Size variation changes drug response

## Sources

- Sutherland, McCredie and Inch 1971, Journal of the National Cancer Institute: growth of multicell spheroids in tissue culture as a model of nodular carcinomas: https://pubmed.ncbi.nlm.nih.gov/5101993/
- Kelm et al. 2003, Biotechnology and Bioengineering: hanging-drop generation of homogeneous multicellular tumour spheroids: https://doi.org/10.1002/bit.10655

## Connected records

- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [Cancer cell line encyclopedias and dependency maps](https://onco.cc/technologies/cancer-cell-line-encyclopedias/), [Patient-derived organoids](https://onco.cc/technologies/organoids/), [Tumour-on-a-chip](https://onco.cc/technologies/tumour-on-chip/)
- companies: [InSphero](https://onco.cc/companies/insphero/)
- terms: [Organoid](https://onco.cc/terms/organoid/)

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