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Biphasic alpha 2 beta 1 Integrin Expression in Breast Cancer Metastasis to Bone

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Autor(es):
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]
Número total de Autores: 5
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 13 JUL 2021.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 13/00798-2 - A matriz extracelular no envelhecimento, no exercício e no microambiente tumoral
Beneficiário:Heloisa Sobreiro Selistre de Araújo
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 19/11437-7 - Mecanismos moleculares de ação das integrinas durante a progressão tumoral e o desenvolvimento de metástases: uma abordagem intercelular
Beneficiário:Heloisa Sobreiro Selistre de Araújo
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/23094-1 - O papel da integrina ±2²1 na metástase óssea em câncer de mama
Beneficiário:Milene Nóbrega de Oliveira Moritz
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado