<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1889-836X</journal-id>
<journal-title><![CDATA[Revista de Osteoporosis y Metabolismo Mineral]]></journal-title>
<abbrev-journal-title><![CDATA[Rev Osteoporos Metab Miner]]></abbrev-journal-title>
<issn>1889-836X</issn>
<publisher>
<publisher-name><![CDATA[Sociedad Española de Investigaciones Óseas y Metabolismo Mineral]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1889-836X2026000200047</article-id>
<article-id pub-id-type="doi">10.20960/revosteoporosmetabminer.00086</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[MINDIN induce modificaciones de la expresión génica de las integrinas en células osteoblásticas y osteocíticas]]></article-title>
<article-title xml:lang="en"><![CDATA[MINDIN as a mediator of tumor-bone interaction: involvement of integrins in prostate cancer metastatic progression]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Álvarez-Carrión]]></surname>
<given-names><![CDATA[Luis]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gutiérrez-Rojas]]></surname>
<given-names><![CDATA[Irene]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ardura]]></surname>
<given-names><![CDATA[Juan A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Alonso]]></surname>
<given-names><![CDATA[Verónica]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Facultad de Medicina. Universidad CEU San Pablo. CEU Universities Departamento de Ciencias Médicas Básicas Laboratorio de Cáncer y Metástasis Óseas (Unidad de Metástasis)]]></institution>
<addr-line><![CDATA[Madrid ]]></addr-line>
<country>Spain</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Instituto de Medicina Molecular Aplicada (IMMA). Facultad de Medicina. Universidad San Pablo-CEU Laboratorio de Fisiopatología Ósea ]]></institution>
<addr-line><![CDATA[Madrid ]]></addr-line>
<country>Spain</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Facultad de Medicina. Universidad San Pablo-CEU. Boadilla del Monte Departamento de Ciencias Médicas Básicas ]]></institution>
<addr-line><![CDATA[Madrid ]]></addr-line>
<country>Spain</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>06</month>
<year>2026</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>06</month>
<year>2026</year>
</pub-date>
<volume>18</volume>
<numero>2</numero>
<fpage>47</fpage>
<lpage>57</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_arttext&amp;pid=S1889-836X2026000200047&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_abstract&amp;pid=S1889-836X2026000200047&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_pdf&amp;pid=S1889-836X2026000200047&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen 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 &#946;6 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 &#946;6, mientras que el silenciamiento de MINDIN redujo significativamente su expresión. En células osteoblásticas (MC3T3-E1), MINDIN también indujo sobreexpresión de la integrina &#946;6. En contraste, en las células osteocíticas (MLO-Y4), MINDIN no indujo sobrexpresión de &#946;6, sino que incrementó la expresión de la integrina &#945;2. 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 &#946;6.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[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 &#946;6 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 &#946;6 expression, whereas MINDIN silencing significantly reduced its expression. In osteoblastic cells (MC3T3-E1), MINDIN also induced overexpression of integrin &#946;6. In contrast, in osteocytic cells (MLO-Y4), MINDIN did not induce &#946;6 overexpression, but instead increased integrin &#945;2 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 &#946;6.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[MINDIN]]></kwd>
<kwd lng="es"><![CDATA[Integrinas]]></kwd>
<kwd lng="es"><![CDATA[Cáncer de próstata]]></kwd>
<kwd lng="es"><![CDATA[Metástasis óseas]]></kwd>
<kwd lng="en"><![CDATA[MINDIN]]></kwd>
<kwd lng="en"><![CDATA[Integrins]]></kwd>
<kwd lng="en"><![CDATA[Prostate cancer]]></kwd>
<kwd lng="en"><![CDATA[Bone metastases]]></kwd>
</kwd-group>
</article-meta>
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