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Figure 11.3 Carcinoma cells are chemotactic to EGF in the primary tumour. (Left)
Method for using microneedles for in vivo cell collection. Microneedles (i.d. 102 mm) filled
with matrigel and buffer, 25 nM EGF, or 10% FBS are placed in 25-gauge guide needles
that are inserted into the primary tumour of an anesthetized animal. (Right) Carcinoma
cells of metastatic (MTLn3) tumours are more ecient than those in nonmetastatic (MTC)
tumors at entering the matrigel-containing needles. Maximal response is for cells from
MTLn3-generated tumours into EGF- and serum-containing needles. All counts were
normalized to MTC cells collected with matrigel in buffer. Error bar ΒΌ SEM for 4
experiments. (This figure is taken from Wyckoff et al., 2000)
enhanced by the presence of EGF and serum, and is increased in tumours with
high metastatic potential (Wyckoff et al., 2000). The conclusion is that the
EGF-stimulated chemotaxis of carcinoma cells in the primary tumour is
causative for the invasion of the tumour and its metastasis.
Events that define the leading edge during chemotaxis
Hints about how cells read gradients of chemoattractant have been
traditionally derived from work with chemotactic amoeboid cells like
neutrophils and Dictyostelium. Much of the recent work with these cell
types implicates phosphoinositide 3-kinase (PI3K) signalling pathways as
essential in defining cell polarity during chemotaxis (Servant et al., 2000;
Funamoto et al., 2002; Iijima and Devreotes, 2002) (see Chapter by Firtel).
Shallow gradients of chemoattractant are amplified and stabilized by the
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