Abstract
Numerous studies have demonstrated the importance of altered hyaluronan metabolism to malignant progression of multiple tumor types, including breast carcinomas. Increased hyaluronan (HA) metabolism in the stroma of primary tumors promotes activation of oncogenic signaling pathways that impact tumor initiation, growth, and invasion. Carcinoma cell synthesis and assembly of HA-rich pericellular matrices induces a stromal-independent phenotype, which is associated with cancer progression. Although the pro-tumorigenic role of stromal HA is well established, a novel but unexplored hypothesis is that carcinoma cell-associated HA pericellular matrices promote metastasis of circulating tumor cells. Here, we report the development of an in vitro assay that employs microfluidic techniques to directly measure the importance of an HA-rich pericellular matrix in the entry of carcinoma cells into ectopic sites. This model provides the capability to visualize specific steps in metastasis, which is difficult using animal models. The results show that the presence of a HA-rich pericellular matrix correlates to the invasive and metastatic potential of breast carcinoma cells. Furthermore, enzymatic removal or pharmacologic inhibition of HA synthesis significantly inhibits carcinoma cell extravasation and invasion in this model system. These results implicate pericellular HA-rich carcinoma cell associated pericellular matrices in colonization of ectopic sites by circulating tumor cells and support specific targeting of this matrix to limit metastasis in patients.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 242-252 |
| Number of pages | 11 |
| Journal | Integrative Biology (United Kingdom) |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2018 |
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In vitro elucidation of the role of pericellular matrix in metastatic extravasation and invasion of breast carcinoma cells. / Brett, Marie Elena; Bomberger, Heather E.; Doak, Geneva R.; Price, Matthew A.; McCarthy, James B.; Wood, David K.
In: Integrative Biology (United Kingdom), Vol. 10, No. 4, 04.2018, p. 242-252.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vitro elucidation of the role of pericellular matrix in metastatic extravasation and invasion of breast carcinoma cells
AU - Brett, Marie Elena
AU - Bomberger, Heather E.
AU - Doak, Geneva R.
AU - Price, Matthew A.
AU - McCarthy, James B.
AU - Wood, David K.
PY - 2018/4
Y1 - 2018/4
N2 - Numerous studies have demonstrated the importance of altered hyaluronan metabolism to malignant progression of multiple tumor types, including breast carcinomas. Increased hyaluronan (HA) metabolism in the stroma of primary tumors promotes activation of oncogenic signaling pathways that impact tumor initiation, growth, and invasion. Carcinoma cell synthesis and assembly of HA-rich pericellular matrices induces a stromal-independent phenotype, which is associated with cancer progression. Although the pro-tumorigenic role of stromal HA is well established, a novel but unexplored hypothesis is that carcinoma cell-associated HA pericellular matrices promote metastasis of circulating tumor cells. Here, we report the development of an in vitro assay that employs microfluidic techniques to directly measure the importance of an HA-rich pericellular matrix in the entry of carcinoma cells into ectopic sites. This model provides the capability to visualize specific steps in metastasis, which is difficult using animal models. The results show that the presence of a HA-rich pericellular matrix correlates to the invasive and metastatic potential of breast carcinoma cells. Furthermore, enzymatic removal or pharmacologic inhibition of HA synthesis significantly inhibits carcinoma cell extravasation and invasion in this model system. These results implicate pericellular HA-rich carcinoma cell associated pericellular matrices in colonization of ectopic sites by circulating tumor cells and support specific targeting of this matrix to limit metastasis in patients.
AB - Numerous studies have demonstrated the importance of altered hyaluronan metabolism to malignant progression of multiple tumor types, including breast carcinomas. Increased hyaluronan (HA) metabolism in the stroma of primary tumors promotes activation of oncogenic signaling pathways that impact tumor initiation, growth, and invasion. Carcinoma cell synthesis and assembly of HA-rich pericellular matrices induces a stromal-independent phenotype, which is associated with cancer progression. Although the pro-tumorigenic role of stromal HA is well established, a novel but unexplored hypothesis is that carcinoma cell-associated HA pericellular matrices promote metastasis of circulating tumor cells. Here, we report the development of an in vitro assay that employs microfluidic techniques to directly measure the importance of an HA-rich pericellular matrix in the entry of carcinoma cells into ectopic sites. This model provides the capability to visualize specific steps in metastasis, which is difficult using animal models. The results show that the presence of a HA-rich pericellular matrix correlates to the invasive and metastatic potential of breast carcinoma cells. Furthermore, enzymatic removal or pharmacologic inhibition of HA synthesis significantly inhibits carcinoma cell extravasation and invasion in this model system. These results implicate pericellular HA-rich carcinoma cell associated pericellular matrices in colonization of ectopic sites by circulating tumor cells and support specific targeting of this matrix to limit metastasis in patients.
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UR - http://www.scopus.com/inward/citedby.url?scp=85045935466&partnerID=8YFLogxK
U2 - 10.1039/c7ib00173h
DO - 10.1039/c7ib00173h
M3 - Article
C2 - 29623978
AN - SCOPUS:85045935466
VL - 10
SP - 242
EP - 252
JO - Integrative Biology (United Kingdom)
JF - Integrative Biology (United Kingdom)
SN - 1757-9694
IS - 4
ER -