Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, a major cause of mortality, is not yet understood. It is previously identified that the composition and stiffness of alginate-based hydrogels mimicking normal (1-2 kPa) and cancerous (6-10 kPa) breast tissue govern phenotype of breast cancer cells (including MDA-MB-231) in vitro. Here, to understand the causal effect of primary tumor stiffness on metastatic potential, a new breast-to-bone in vitro model is described. Together with alginate-gelatin hydrogels to mimic breast tissue, 3D printed biohybrid poly-caprolactone (PCL)-composite scaffolds, decellularized following bone-ECM deposition through Saos-2 engraftment, are used to mimic the bone tissue. It is reported that higher hydrogel stiffness results in the increased migration and invasion capacity of MDA-MB 231 cells. Interestingly, increased expression of osteolytic factors PTHrP and IL-6 is observed when MDA-MB-231 cells pre-conditioned in stiffer hydrogels (10 kPa, 3% w/v gelatin) colonize the bone/PCL scaffolds. The new breast-to-bone in vitro models herein described are designed with relevant tissue microenvironmental factors and could emerge as future non-animal technological platforms for monitoring metastatic processes and therapeutic efficacy.

Invasion and Secondary Site Colonization as a Function of In Vitro Primary Tumor Matrix Stiffness: Breast to Bone Metastasis / Shah, Lekha; Latif, Ayşe; Williams, Kaye J; Mancuso, Elena; Tirella, Annalisa. - In: ADVANCED HEALTHCARE MATERIALS. - ISSN 2192-2659. - 12:3(2022), p. 2201898. [10.1002/adhm.202201898]

Invasion and Secondary Site Colonization as a Function of In Vitro Primary Tumor Matrix Stiffness: Breast to Bone Metastasis

Shah, Lekha
Primo
;
Tirella, Annalisa
Ultimo
2022-01-01

Abstract

Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, a major cause of mortality, is not yet understood. It is previously identified that the composition and stiffness of alginate-based hydrogels mimicking normal (1-2 kPa) and cancerous (6-10 kPa) breast tissue govern phenotype of breast cancer cells (including MDA-MB-231) in vitro. Here, to understand the causal effect of primary tumor stiffness on metastatic potential, a new breast-to-bone in vitro model is described. Together with alginate-gelatin hydrogels to mimic breast tissue, 3D printed biohybrid poly-caprolactone (PCL)-composite scaffolds, decellularized following bone-ECM deposition through Saos-2 engraftment, are used to mimic the bone tissue. It is reported that higher hydrogel stiffness results in the increased migration and invasion capacity of MDA-MB 231 cells. Interestingly, increased expression of osteolytic factors PTHrP and IL-6 is observed when MDA-MB-231 cells pre-conditioned in stiffer hydrogels (10 kPa, 3% w/v gelatin) colonize the bone/PCL scaffolds. The new breast-to-bone in vitro models herein described are designed with relevant tissue microenvironmental factors and could emerge as future non-animal technological platforms for monitoring metastatic processes and therapeutic efficacy.
2022
3
Shah, Lekha; Latif, Ayşe; Williams, Kaye J; Mancuso, Elena; Tirella, Annalisa
Invasion and Secondary Site Colonization as a Function of In Vitro Primary Tumor Matrix Stiffness: Breast to Bone Metastasis / Shah, Lekha; Latif, Ayşe; Williams, Kaye J; Mancuso, Elena; Tirella, Annalisa. - In: ADVANCED HEALTHCARE MATERIALS. - ISSN 2192-2659. - 12:3(2022), p. 2201898. [10.1002/adhm.202201898]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/376567
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