MINDIN induce modificaciones de la expresión génica de las integrinas en células osteoblásticas y osteocíticas.

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Bibliographic Details
Title:	MINDIN induce modificaciones de la expresión génica de las integrinas en células osteoblásticas y osteocíticas.
Alternate Title:	MINDIN as a mediator of tumor-bone interaction: involvement of integrins in prostate cancer metastatic progression.
Authors:	Álvarez-Carrión, Luis^1,2, Gutiérrez-Rojas, Irene¹, Ardura, Juan A.^2,3, Alonso, Verónica^1,2 veronica.alonsorodriguez@ceu.es
Source:	Journal of Osteoporosis & Mineral Metabolism / Revista de Osteoporosis y Metabolismo Mineral (Spanish edition). Apr-Jun2026, Vol. 18 Issue 2, p47-57. 11p.
Subjects:	Integrins, Bone metastasis, Prostate cancer, Tumor microenvironment, Osteoblasts, Osteocytes
Abstract (English):	Bone is a dynamic organ subjected to constant remodeling, a process that depends on the coordinated activity of osteoblasts, osteoclasts, and osteocytes. Bone is also a common site of metastasis for solid tumors, as occurs in prostate cancer, whose bone metastasis is associated with a poor prognosis. Furthermore, it has been proposed that, before the establishment of metastases, tumors induce changes in distant organs, promoting the formation of premetastatic niches that favor tumor implantation. MINDIN, an extracellular matrix protein, has been identified as a potential biomarker of prostate cancer and is highly expressed in patients with bone metastases. This protein can modify both tumor cells and the bone environment, and it has been suggested that it may promote tumor growth and metastatic dissemination. MINDIN may also act as a ligand for integrins, a family of transmembrane receptors that play a key role in the regulation of tumor cell adhesion, signaling, and migration. Based on these observations, we hypothesized that MINDIN may promote the formation of the bone premetastatic niche through the modification of specific integrin expression in tumor and bone cells. A murine tumor model was used to study the influence of MINDIN on integrin expression and its possible involvement in the formation of the bone premetastatic niche, together with in vitro experimental models employing osteoblastic (MC3T3-E1), osteocytic (MLO-Y4), and prostate tumor (TRAMP-C1) cell lines. In the experimental animal model previously developed by our group, in which a primary tumor was established in the absence of overt bone metastases, an increase in integrin β6 gene expression was observed in both the prostates and tibias of tumor-bearing mice, an effect that was reversed by MINDIN silencing. These data were confirmed in our in vitro experimental model, where TRAMP-C1 cells stimulated with MINDIN showed increased integrin β6 expression, whereas MINDIN silencing significantly reduced its expression. In osteoblastic cells (MC3T3-E1), MINDIN also induced overexpression of integrin β6. In contrast, in osteocytic cells (MLO-Y4), MINDIN did not induce β6 overexpression, but instead increased integrin α2 expression. These results suggest possible cell-specificity in the interaction between MINDIN and integrins, where MINDIN may favor the creation of premetastatic niches in bone through the overexpression of integrin β6. [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	El hueso es un órgano dinámico sometido a constante remodelación, proceso que depende de la actividad coordinada de osteoblastos, osteoclastos y osteocitos. El hueso también es un sitio común de metástasis de tumores sólidos, como ocurre en el cáncer de próstata, cuya metástasis ósea se asocia con un pronóstico grave. Además, se ha propuesto que antes del establecimiento de metástasis, los tumores inducen cambios en órganos distantes, promoviendo la formación de nichos premetastásicos que favorecen la implantación tumoral. MINDIN, una proteína de matriz extracelular ha sido identificada como un biomarcador potencial del cáncer de próstata y se encuentra altamente expresada en pacientes con metástasis óseas. Esta proteína puede modificar tanto a las células tumorales como al entorno óseo, y se ha sugerido que pueda favorecer el crecimiento tumoral y la diseminación metastásica. MINDIN también puede actuar como un ligando para integrinas, una familia de receptores transmembrana clave en la regulación de adhesión, señalización y migración de células tumorales. Basándonos en estas observaciones, hipotetizamos que MINDIN puede promover la formación del nicho premetastásico óseo mediante la modificación de expresión de integrinas específicas en células tumorales y óseas. Se empleó un modelo murino tumoral para estudiar la influencia de MINDIN en la expresión de integrinas y su posible implicación en la formación del nicho premetastásico óseo, así como experimentación en modelos in vitro donde se emplearon líneas celulares osteoblásticas (MC3T3-E1), osteocíticas (MLO-Y4) y tumorales prostáticas (TRAMP-C1). En el modelo experimental animal previamente desarrollado por nuestro grupo donde se estableció tumor primario con ausencia de metástasis óseas establecidas, se observó un aumento de la expresión génica de la integrina β6 tanto en las próstatas como en las tibias de ratones con presencia de tumor, efecto que se revirtió con el silenciamiento de MINDIN. Estos datos fueron confirmados en nuestro modelo experimental in vitro, donde las células TRAMP-C1 estimuladas con MINDIN mostraron un aumento en la expresión de la integrina β6, mientras que el silenciamiento de MINDIN redujo significativamente su expresión. En células osteoblásticas (MC3T3-E1), MINDIN también indujo sobreexpresión de la integrina β6. En contraste, en las células osteocíticas (MLO-Y4), MINDIN no indujo sobrexpresión de β6, sino que incrementó la expresión de la integrina α2. Estos resultados sugieren una posible especificidad celular en la interacción entre MINDIN e integrinas, donde MINDIN podría favorecer la creación de nichos premetastásicos en hueso mediante la sobreexpresión de la integrina β6. [ABSTRACT FROM AUTHOR]
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Database:	MedicLatina

Description
Abstract:	Bone is a dynamic organ subjected to constant remodeling, a process that depends on the coordinated activity of osteoblasts, osteoclasts, and osteocytes. Bone is also a common site of metastasis for solid tumors, as occurs in prostate cancer, whose bone metastasis is associated with a poor prognosis. Furthermore, it has been proposed that, before the establishment of metastases, tumors induce changes in distant organs, promoting the formation of premetastatic niches that favor tumor implantation. MINDIN, an extracellular matrix protein, has been identified as a potential biomarker of prostate cancer and is highly expressed in patients with bone metastases. This protein can modify both tumor cells and the bone environment, and it has been suggested that it may promote tumor growth and metastatic dissemination. MINDIN may also act as a ligand for integrins, a family of transmembrane receptors that play a key role in the regulation of tumor cell adhesion, signaling, and migration. Based on these observations, we hypothesized that MINDIN may promote the formation of the bone premetastatic niche through the modification of specific integrin expression in tumor and bone cells. A murine tumor model was used to study the influence of MINDIN on integrin expression and its possible involvement in the formation of the bone premetastatic niche, together with in vitro experimental models employing osteoblastic (MC3T3-E1), osteocytic (MLO-Y4), and prostate tumor (TRAMP-C1) cell lines. In the experimental animal model previously developed by our group, in which a primary tumor was established in the absence of overt bone metastases, an increase in integrin β6 gene expression was observed in both the prostates and tibias of tumor-bearing mice, an effect that was reversed by MINDIN silencing. These data were confirmed in our in vitro experimental model, where TRAMP-C1 cells stimulated with MINDIN showed increased integrin β6 expression, whereas MINDIN silencing significantly reduced its expression. In osteoblastic cells (MC3T3-E1), MINDIN also induced overexpression of integrin β6. In contrast, in osteocytic cells (MLO-Y4), MINDIN did not induce β6 overexpression, but instead increased integrin α2 expression. These results suggest possible cell-specificity in the interaction between MINDIN and integrins, where MINDIN may favor the creation of premetastatic niches in bone through the overexpression of integrin β6. [ABSTRACT FROM AUTHOR]
ISSN:	1889836X
DOI:	10.20960/RevOsteoporosMetabMiner.00086