Solid stress facilitates spheroid formation: potential involvement of hyaluronan

Area of Science:

• Biophysics
• Cancer Biology
• Biomaterials

Background:

• Neoplastic cells generate solid stress when confined.
• Previous studies showed solid stress inhibits spheroid growth (45-120 mmHg).
• Metastatic cancer cells exhibit varied spheroid formation behaviors.

Purpose of the Study:

• Investigate solid stress's role in spheroid formation for metastatic Dunning R3327 rat prostate carcinoma AT3.1 cells.
• Compare spheroid formation and morphology between high (AT3.1) and low (AT2.1) metastatic variants.
• Elucidate the influence of cell-matrix interactions and hyaluronan in spheroid development.

Main Methods:

• Culturing multicellular spheroids in agarose gels with defined mechanical properties.
• Utilizing enzymatic gel digestion to relieve solid stress.
• Histological examination and hyaluronan staining of spheroids.

Main Results:

• Solid stress facilitated spheroid formation in AT3.1 cells, which typically do not form spheroids in suspension.
• Increased solid stress reduced AT3.1 spheroid size and growth rate.
• Relieving stress caused AT3.1 spheroids to lose morphology; AT2.1 spheroids retained it.
• AT3.1 spheroids contained hyaluronan in the matrix, unlike suspension-grown cells; AT2.1 spheroids had hyaluronan in both conditions.

Conclusions:

• Solid stress is crucial for spheroid formation when cell-matrix adhesion predominates, as seen in AT3.1 cells.
• Cell-cell adhesion may suffice for spheroid formation when solid stress is absent.
• Findings suggest solid stress influences tumor growth, invasion, and metastasis.
• Hyaluronan presence correlates with spheroid formation under solid stress.