| Full text | |
| Author(s): |
Moritz, Milene N. O.
[1, 2]
;
Merkel, Alyssa R.
[2, 3]
;
Feldman, Ean G.
[4]
;
Selistre-de-Araujo, Heloisa S.
[5, 1]
;
Rhoades (Sterling), Julie A.
[2, 3, 6, 7]
Total Authors: 5
|
| Affiliation: | [1] Univ Fed Sao Carlos, Program Evolutionary Genet & Mol Biol, BR-13565905 Sao Carlos, SP - Brazil
[2] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN 37232 - USA
[3] Vanderbilt Univ, Med Ctr, Ctr Bone Biol, Nashville, TN 37232 - USA
[4] Vanderbilt Univ, Med Ctr, Vanderbilt Grad Sch Program Biomed Sci, Nashville, TN 37232 - USA
[5] Univ Fed Sao Carlos, Dept Physiol Sci, BR-13565905 Sao Carlos, SP - Brazil
[6] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 - USA
[7] Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN 37232 - USA
Total Affiliations: 7
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 13 JUL 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
Integrins participate in the pathogenesis and progression of tumors at many stages during the metastatic cascade. However, current evidence for the role of integrins in breast cancer progression is contradictory and seems to be dependent on tumor stage, differentiation status, and microenvironmental influences. While some studies suggest that loss of alpha 2 beta 1 enhances cancer metastasis, other studies suggest that this integrin is pro-tumorigenic. However, few studies have looked at alpha 2 beta 1 in the context of bone metastasis. In this study, we aimed to understand the role of alpha 2 beta 1 integrin in breast cancer metastasis to bone. To address this, we utilized in vivo models of breast cancer metastasis to bone using MDA-MB-231 cells transfected with an alpha 2 expression plasmid (MDA-OE alpha 2). MDA cells overexpressing the alpha 2 integrin subunit had increased primary tumor growth and dissemination to bone but had no change in tumor establishment and bone destruction. Further in vitro analysis revealed that tumors in the bone have decreased alpha 2 beta 1 expression and increased osteolytic signaling compared to primary tumors. Taken together, these data suggest an inverse correlation between alpha 2 beta 1 expression and bone-metastatic potential. Inhibiting alpha 2 beta 1 expression may be beneficial to limit the expansion of primary tumors but could be harmful once tumors have established in bone. (AU) | |
| FAPESP's process: | 13/00798-2 - The extracellular matrix in aging, exercise and in the tumor microenvironment |
| Grantee: | Heloisa Sobreiro Selistre de Araújo |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/11437-7 - Integrin molecular mechanisms of action during tumor progression and metastasis development: an intercellular approach |
| Grantee: | Heloisa Sobreiro Selistre de Araújo |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/23094-1 - The role of integrin ±2²1 in breast cancer metastasis to bone |
| Grantee: | Milene Nóbrega de Oliveira Moritz |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |