Stage-dependent regulation of mammary ductal branching by heparan sulfate and HGF-cMet signaling

Garner, Omai B.; Bush, Kevin T.; Nigam, Kabir B.; Yamaguchi, Yu; Xu, Ding; Nigám, Sanjay K.

doi:10.1016/j.ydbio.2011.04.035

Cited by 45 publications

(42 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We find that through COL, branching is induced and directed between acini, rather than spontaneously arising at individual acini. This nonautonomous behavior is different from what is observed in chemical-induced branching, i.e., individual acini form branching in direct response to morphogens (35,36). Nonautonomous behavior has also been observed in autocrine-regulated branching processes, where individual cells secrete inhibitory morphogens (such as TGF-β) to suppress branching at each other (37).…”

Section: Discussionmentioning

confidence: 91%

Long-range mechanical force enables self-assembly of epithelial tubular patterns

Guo

Ouyang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

102

View full text Add to dashboard Cite

Enabling long-range transport of molecules, tubules are critical for human body homeostasis. One fundamental question in tubule formation is how individual cells coordinate their positioning over long spatial scales, which can be as long as the sizes of tubular organs. Recent studies indicate that type I collagen (COL) is important in the development of epithelial tubules. Nevertheless, how cell-COL interactions contribute to the initiation or the maintenance of long-scale tubular patterns is unclear. Using a two-step process to quantitatively control cell-COL interaction, we show that epithelial cells developed various patterns in response to fine-tuned percentages of COL in ECM. In contrast with conventional thoughts, these patterns were initiated and maintained by traction forces created by cells but not diffusive factors secreted by cells. In particular, COL-dependent transmission of force in the ECM led to long-scale (up to 600 μm) interactions between cells. A mechanical feedback effect was encountered when cells used forces to modify cell positioning and COL distribution and orientations. Such feedback led to a bistability in the formation of linear, tubule-like patterns. Using micro-patterning technique, we further show that the stability of tubule-like patterns depended on the lengths of tubules. Our results suggest a mechanical mechanism that cells can use to initiate and maintain long-scale tubular patterns.tubulogenesis | biomechanics | morphogenesis T o enable long-range bulk transport of liquid and gas, tubules are the most commonly used form of tissue architecture in our bodies. Examples where tubules are used include lung, mammary gland, blood vessels, salivary gland, and kidney (1-4). Tubule formation requires aligning the positions of individual cells (of size approximately 10-20 microns) over long spatial scales (from hundreds of microns to centimeters, i.e., the size of organs). Although current studies focus on how genetics and morphogens control tubule formation (5-10), ECM molecules are also known to be important in the patterning of tubular structures (11-15). In particular, normal epithelia are surrounded by two ECM components: basement membrane (BM) and type I collagen (COL) (16, 17), with COL fibers frequently found around epithelial tubules, e.g., the milk ducts in the mammary gland (18). Accordingly, adding collagenase or stimulating COL expression in the ECM perturbs epithelial tubular growth (13,19,20). Nevertheless, how cell-COL interactions contribute to the initiation or the maintenance of long-scale tubular patterns is unclear.Here, we quantitatively study how cells change their morphology in response to the presence of COL in the ECM and how such morphogenetic changes lead to the formation of long-scale tubular patterns. Previous studies showed that breast epithelial cells developed long-scale tubules (length ≥ 400 μm) in COL gels (21, 22), whereas they formed globular acini (diameter approximately 100 μm) in BM gels (23,24). We thus developed a two-step process to control cel...

show abstract

Section: Discussionmentioning

confidence: 91%

Long-range mechanical force enables self-assembly of epithelial tubular patterns

Guo

Ouyang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

102

View full text Add to dashboard Cite

show abstract

“…Floxed allele: altered lipoprotein clearance in AlbCre mice ; altered branching morphogenesis in the mammary gland (Garner et al 2011). …”

Section: H2stmentioning

confidence: 99%

Heparan Sulfate Proteoglycans

Sarrazin¹,

Lamanna²,

Esko

2011

Cold Spring Harbor Perspectives in Biology

1,251

1,238

View full text Add to dashboard Cite

“…This is a non-autonomous behavior. It is different from those observed in chemicalinduced branching, where individual cells form branching in response to morphogens or growth factors such as hepatocyte growth factor and epidermal growth factor [24][25][26][27]. Non-autonomous behavior has also been observed in autocrine-regulated branching processes where individual cells secrete inhibitory morphogens (such as TGF-to suppress branching at each other [28].…”

Section: Synergistic Effects In Branching and Invasionmentioning

confidence: 92%

Long-range mechanical force in colony branching and tumor invasion

Guo

Ouyang

et al. 2011

SPIE Proceedings

View full text Add to dashboard Cite

The most concerned factors for cancer prognosis are tumor invasion and metastasis. The patterns of tumor invasion can be characterized as random infiltration to surrounding extracellular matrix (ECM) or formation of long-range path for collective migration. Recent studies indicate that mechanical force plays an important role in tumor infiltration and collective migration. However, how tumor colonies develop mechanical interactions with each other to initiate various invasion patterns is unclear. Using a micro-patterning technique, we partition cells into clusters to mimic tumor colonies and quantitatively induce colony-ECM interactions. We find that pre-malignant epithelial cells, in response to concentrations of type I collagen in ECM ([COL]), develop various branching patterns resembling those observed in tumor invasion. In contrast with conventional thought, these patterns require long-range (~ 600 m) transmission of traction force, but not biochemical factors. At low [COL], cell colonies synergistically develop pairwise and directed branching mimicking the formation of long-range path. By contrast, at high [COL] or high colony density, cell colonies develop random branching and scattering patterns independent of each other. Our results suggest that tumor colonies might select different invasive patterns depending on their interactions with each other and with the ECM.

show abstract

Stage-dependent regulation of mammary ductal branching by heparan sulfate and HGF-cMet signaling

Cited by 45 publications

References 90 publications

Long-range mechanical force enables self-assembly of epithelial tubular patterns

Long-range mechanical force enables self-assembly of epithelial tubular patterns

Heparan Sulfate Proteoglycans

Long-range mechanical force in colony branching and tumor invasion

Contact Info

Product

Resources

About