Probing the Biophysical Properties of Primary Breast Tumor-Derived Fibroblasts

Alcoser, Turi A.; Bordeleau, François; Carey, Shawn P.; Lampi, Marsha C.; Kowal, Daniel R.; Somasegar, Sahana; Varma, Sonal; Shin, Sandra J.; Reinhart‐King, Cynthia A.

doi:10.1007/s12195-014-0360-9

Cited by 21 publications

(19 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results provide new insights into how tumor cell-shed MVs can influence the microenvironment by promoting ECM reorganization. Specifically, we showed that MVs from cancer cells increased epithelial cell contractility, which is known to be required for ECM remodeling and reorganization (Alcoser et al, 2014; Yamaguchi et al, 2014). Interestingly, tumor shed MVs can also mediate the transformation of fibroblasts into cancer associated fibroblasts (Webber et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, tumor shed MVs can also mediate the transformation of fibroblasts into cancer associated fibroblasts (Webber et al, 2010). Notably, cancer associated fibroblasts are highly contractile cells that play a major role in ECM remodeling (Alcoser et al, 2014; Cukierman and Bassi, 2010; Dumont et al, 2013; Mao et al, 2013; Webber et al, 2010). In our case, the effect observed with non-malignant epithelial cells indicates that MVs can promote ECM reorganization in vitro ..…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility

Bordeleau

Chan

Antonyak

et al. 2016

Journal of Biomechanics

Self Cite

View full text Add to dashboard Cite

During tumor progression, cancer cells interact and communicate with non-malignant cells within their local microenvironment. Microvesicles (MV) derived from human cancer cells play an important role in mediating this communication. Another critical aspect of cancer progression involves widespread ECM remodeling, which occur both at the primary and metastatic sites. ECM remodeling and reorganization within the tumor microenvironment is generally attributed to fibroblasts. Here, using MCF10a cells, a well-characterized breast epithelial cell line that exhibits a non-malignant epithelial phenotype, and MVs shed by aggressive MDA-MB-231 carcinoma cells, we show that non-malignant epithelial cells can participate in ECM reorganization of 3D collagen matrices following their treatment with cancer cell-derived MVs. In addition, MVs trigger several changes in epithelial cells under 3D culture conditions. Furthermore, we show that this ECM reorganization is associated with an increase in cellular traction force following MV treatment, higher acto-myosin contractility, and higher FAK activity. Overall, our findings suggests that MVs derived from tumor cells can contribute to ECM reorganization occurring within the tumor microenvironment by enhancing the contractility of non-malignant epithelial cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility

Bordeleau

Chan

Antonyak

et al. 2016

Journal of Biomechanics

Self Cite

View full text Add to dashboard Cite

show abstract

“…The inclusion of multiple cell types is not limited to tumorigenic cells, but extends to secondary cell types as well, typically CAFs and TAMs. There are a few reports of stromal spheroid models that do not include malignant cells such as collagen embedded CAF spheroids or non‐embedded TAM‐invaded CAF spheroids . However the most prevalent model iteration combines malignant cells with its analogous stromal cells.…”

Section: Embedded Spheroid Modelsmentioning

confidence: 99%

Embedded Spheroids as Models of the Cancer Microenvironment

2017

View full text Add to dashboard Cite

To more accurately study the complex mechanisms behind cancer invasion, progression, and response to treatment, researchers require models that replicate both the multicellular nature and 3D stromal environment present in an in vivo tumor. Multicellular aggregates (i.e., spheroids) embedded in an extracellular matrix mimic are a prevalent model. Recently, quantitative metrics that fully utilize the capability of spheroids are described along with conventional experiments, such as invasion into a matrix, to provide additional details and insights into the underlying cancer biology. The review begins with a discussion of the salient features of the tumor microenvironment, introduces the early work on non-embedded spheroids as tumor models, and then concentrates on the successes achieved with the study of embedded spheroids. Examples of studies include cell movement, drug response, tumor cellular heterogeneity, stromal effects, and cancer progression. Additionally, new methodologies and those borrowed from other research fields (e.g., vascularization and tissue engineering) are highlighted that expand the capability of spheroids to aid future users in designing their cancer-related experiments. The convergence of spheroid research among the various fields catalyzes new applications and leads to a natural synergy. Finally, the review concludes with a reflection and future perspectives for cancer spheroid research.

show abstract

“…CAFs acquire an activated phenotype with enhanced expression of a-SMA, increased cell contractility and spindle shape resembling myofibroblast phenotypes commonly observed in wounds (5). CAF activation occurs in the stroma during the early stage of breast cancer where tissue stiffness is relatively low (6). In a twodimensional (2D) culture system mimicking stiff matrix conditions, myofibroblast differentiation has been well established (7).…”

Section: Introductionmentioning

confidence: 99%

SPIN90 Depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression

et al. 2017

View full text Add to dashboard Cite

Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. .

show abstract

Probing the Biophysical Properties of Primary Breast Tumor-Derived Fibroblasts

Cited by 21 publications

References 42 publications

Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility

Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility

Embedded Spheroids as Models of the Cancer Microenvironment

SPIN90 Depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression

Contact Info

Product

Resources

About