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LAMININ-521 and LAMININ-332

 
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PROTOCOLS

Culture of U251 glioblastoma cells on laminin substrates


APPLICATION NOTES

Cancer stem cell culture on laminin cell culture substrates


CUSTOMER TESTIMONIALS        

HOW TO CULTURE CANCER STEM CELLS ON LAMININ SUBSTRATES

How to culture cancer stam cells on laminin substratesCancer cells use laminin/integrin signaling pathways that promote tumor cell growth, invasion and metastasis

During the past decades, many studies have provided evidence for a role of laminin-binding integrins in tumorigenesis, both tumor-promoting and suppressive activities. As a major component of the basement membrane that forms the stem cell niche (Rodin, 2014) and because of the central role in the regulation of cancer stem cells (Qin, 2016), laminin/integrin-mediated interactions is of high therapeutic interest in cancer treatment (Rabinovitz & Mercurio, 1997; Berg, 2016). Cancer stem cells (CSCs) represent a subset of tumor cells that typically exhibit the ability to self-renewal and often have multi-potent capabilities. The expression of various laminin subunits in the tumor microenvironment surrounding the CSCs subpopulation has been demonstrated to serve as a niche for CSCs and contribute to tumor progression (Qin, 2016).

 

A prominent role for laminin in the cancer stem cell niche

Laminin-332 has been shown to be a molecular marker for cells with invasive properties and correlated with poor prognosis (Kang, 2013; Rani, 2013). Laminin-332 is known to support the stable anchoring of basal keratinocytes to the epidermal basement membrane via hemidesmosomes components and the α6β4 integrin (Ghohestani, 2001; Litjens, 2006; Nishiuchi, 2006). However, laminin-332 is also an important motility factor for wound healing as well as for melanoma cancer invasion (Kariya, 2012). Prostate cancer cells have also been shown to bind to laminin-332 via integrin α6β4 that activate signaling pathways promoting tumor cell growth, invasion, and metastasis (Berg, 2016). Govaere and co-workers identified a prominent role for laminin-332 as part of the stem cell nice in human hepatic tumors where laminin-332 promotes stemness and protects the hepatic cancer cells against chemotherapy (Govaere, 2015).

Chang et al. show that breast cancer stem cells produce alpha-5 laminin matrix (laminin-521 and laminin-511) that promotes self-renewal and tumor initiation via α6β1 integrin interaction and activation of the Hippo transducer TAZ. TAZ also regulates the transcription of alpha-5 laminin, establishing a positive feedback loop that contributes to stemness in breast cancer (Chang, 2014).

In a publication by Fennewald et al., the authors showed that head and neck squamous cell carcinoma cell lines bind to laminin-511 under lymphodynamic low shear stress (consistent with lymph flow), mediated by β1 integrins interactions (Fennewald, 2012).

A publication by Kaemmerer et al. shows that ovarian cancer cells cultured GelMA/laminin-411 spheroids result in higher reproducibility, less complexity and better comparability between different groups than traditional cell monolayer. The culture of ovarian cancer cells in GelMA/laminin-411 spheroids results in higher reproducibility, less complexity and better comparability between different groups than traditional cell monolayer approaches (Kaemmerer2014).

In a publication in Nature Cancer (Ganesh,2020) the authors show that L1CAM+ cells in human colorectal cancer (CRC) have metastasis-initiating capacity, and they define their relationship to tissue regeneration. They confirmed that L1CAM bound heterophilically to laminins known to be expressed in the intestinal and endothelial cell basement membranes in addition to exhibiting homophilic interaction with L1CAM itself. L1CAM knockdown inhibited the ability of CRC organoid-derived cells to bind to laminin-coated plates. Together, these data suggest that L1CAM enables the adhesion of metastasis-initiating cells to laminin-rich basement membranes, which is required for metastasis and organoid growth. Qin et al. (2020) show that also show how basement membrane proteins contribute to tumor progression towards the metastatic stage. The authors show that laminin 521 (LN521) promotes colorectal cancer (CRC) cell self-renewal and invasion. They show that laminin expression is a frequent feature of metastatic dissemination in CRC and promotes cell invasion and self-renewal, the latter through engagement of integrin isoforms and activation of STAT3 signaling.

 

Laminin-521 provides good support for the culture of various tumor cells of the nervous system

Laminin-521 promotes pluripotent stem cell survival, migration and stimulates cell proliferation over differentiation (Miyazaki, 2008; Rodin, 2014). Naturally, laminin-521 has also been shown to provide good support for the culture of various cancer cells, such as neuroblastoma (Persson, 2020), glioblastoma and medulloblastoma cells.


Gene expression analysis of different neuroblastoma cell lines shows high expression of alpha-5 and alpha-4, beta-1 and beta-2 laminin chains, indicating expression of laminin-521, -511, -411 and -421 (unpublished data). Indeed, laminin-521 works well for a culture of neuroblastoma cell lines.

Laminin-521 even supports the culture of medulloblastoma cells which is otherwise difficult to maintain in vitro (unpublished data).

In a publication by Ma et al., the authors showed that alpha-4 and alpha-5 laminins have specific effects in promoting the stemness of glioma cells, both at gene and protein expression levels. In collaboration with a 3D context, U251 glioblastoma cells showed substantially upregulation of integrin α6β4 and enhanced clonogenicity on laminin-521, -511, -421 and -411 (Ma, 2016).

LAMININ KEY ADVANTAGES

  • Laminins are a major component of the basement membrane that forms the stem cell niche

  • Evident role of laminin-binding integrins in tumorigenesis, both tumor-promoting and suppressive activities

  • Laminin-332 has been shown to be a molecular marker for cells with invasive properties and correlated with poor prognosis

  • A prominent role for laminin-332 as part of the stem cell nice in human hepatic tumours, melanoma cancer and prostate cancer

  • Breast cancer stem cells produce laminin-521 and laminin-511 that promotes self-renewal and tumor initiation via α6β1 integrin interaction and activation of the Hippo transducer TAZ

  • Laminin-521 provide good support for the culture of various cancer cells, such as neuroblastoma, glioblastoma and medulloblastoma cells

  • Laminin-521 have specific effects in promoting the stemness of glioma cells, both at gene and protein expression level

  • Defined and animal origin-free cell culture matrix for clinical compliance

  • No lot-to-lot variability for standardized experiments with less variation

  • Scientifically validated in high-impact journals

  • x
  • Expansion of human PSC

  • Mesenchymal stem cells

  • Clonal cell culture applications

  • Eye cells

  • Cardiac cells

  • Neural cells

  • Skeletal muscle cells

  • Kidney cells

  • Hepatic cells

  • Cancer cells

  • Lung cells

  • Animal stem cells

  • Endothelial cells

  • Pancreatic cells

  • Intestinal cells

  • Normal and cancerous mammary cells

  • Epithelial cells

Biolaminin 521 CTG

Biolaminin 521 CTG cell therapy grade cell culture matrix makes pluripotent stem cell culture easy. A defined, animal origin-free and biologically relevant cell culture system for better cell models.

  • x
  • Expansion of human PSC

  • Clonal cell culture applications

  • Eye cells

  • Cardiac cells

  • Neural cells

  • Skeletal muscle cells

  • Kidney cells

  • Hepatic cells

  • Cancer cells

  • Lung cells

  • Animal stem cells

  • Mesenchymal stem cells

  • Endothelial cells

  • Pancreatic cells

  • Intestinal cells

  • Normal and cancerous mammary cells

  • Epithelial cells

Biolaminin 521 MX

Biolaminin 521 MX research-grade cell culture matrix makes pluripotent stem cell culture easy. A defined, animal origin-free and biologically relevant cell culture system for better cell models.

  • x
  • Expansion of human PSC

  • Mesenchymal stem cells

  • Clonal cell culture applications

  • Eye cells

  • Cardiac cells

  • Neural cells

  • Skeletal muscle cells

  • Kidney cells

  • Hepatic cells

  • Cancer cells

  • Lung cells

  • Animal stem cells

  • Endothelial cells

  • Pancreatic cells

  • Intestinal cells

  • Normal and cancerous mammary cells

  • Epithelial cells

Biolaminin 521 LN

Biolaminin 521 LN research-grade cell culture matrix makes pluripotent stem cell culture easy. A defined, animal origin-free and biologically relevant cell culture system for better cell models.